Microchemical Journal 106 (2013) 1–16

Contents lists available at SciVerse ScienceDirect

Microchemical Journal
journal homepage: www.elsevier.com/locate/microc

Review article

Recent applications in derivative ultraviolet/visible absorption

spectrophotometry: 2009–2011
A review
C. Bosch Ojeda, F. Sanchez Rojas ⁎
Department of Analytical Chemistry, Faculty of Sciences, University of Málaga, Campus Teatinos, 29071 Málaga, Spain

a r t i c l e i n f o a b s t r a c t

Article history: Derivative spectrophotometry (DS) has been introduced for the resolution of overlapping peaks. DS method
Received 8 May 2012 has been widely used to enhance the signal and resolve the overlapped peak-signals due to its advantages in
Received in revised form 21 May 2012 differentiating closely adjacent peaks, and identifying weak peaks obscured by sharp peaks.
Accepted 22 May 2012
In this work, the analytical applications of derivative UV/VIS region absorption spectrophotometry produced
Available online 26 May 2012
in the last 3 years (since 2009) are reviewed.
Keywords:
© 2012 Elsevier B.V. All rights reserved.
Derivative UV–vis
Multi-component analysis
Pharmaceutical analysis
Metal ion analysis
Review

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
2. Theoretical and instrumental aspects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
2.1. Method of disturbing effect . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
2.2. Method of sixteen solutions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
3. Applications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
3.1. Inorganic analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
3.2. Pharmaceutical analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
3.3. Stability-indicating methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
3.4. Analysis of biological compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
3.5. Food analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
3.6. Environmental analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
3.7. Other analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
4. The derivative technique as a tool for green analytical chemistry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
5. Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13

1. Introduction
Application of derivative technique of spectrophotometry offers a
powerful tool for quantitative analysis of multi-component mixtures.
When derivatised, the maxima and minima of the original function
⁎ Corresponding author. Tel.: + 34 952137393; fax: + 34 952132000.
E-mail address: fsanchezr@uma.es (F. Sanchez Rojas).
take zero values, and the inflections are converted into maxima or
minima, respectively. The derivative curves are more structured
than the original spectra, thus enabling very tiny differences between
the original spectra to be identified. DS method has been widely used
to enhance the signal and resolve the overlapped peak-signals due to
its advantages in differentiating closely adjacent peaks, and identify-
ing weak peaks obscured by sharp peaks.
The main disadvantage of D is its dependence on instrumental pa-
rameters like speed of scan and the slit width. The instrumental

0026-265X/$ – see front matter © 2012 Elsevier B.V. All rights reserved.
doi:10.1016/j.microc.2012.05.012
2 C. Bosch Ojeda, F. Sanchez Rojas / Microchemical Journal 106 (2013) 1–16
conditions of recording parent zero-order spectrum have strong in-
fluence on the shape and intensity of its derivative generations.
In general, DS has been directly used for the simultaneous deter-
mination of organic and inorganic compounds. Fig. 1 shows the appli-
cations of DS in several areas since last three decades ago. As can be
seen from this figure pharmaceutical and inorganic analyses are two
areas where DS has been more used.
DS offers greater selectivity than normal spectrophotometry in the
simultaneous determination of two or more components without
previous chemical separation. Principles, advantages and applications
of this technique have been reviewed in four works published some
years ago [1–4]. In these works, we exposed the different aspects of
derivative ultraviolet/visible spectrophotometry: theoretical, instru-
mental devices and analytical applications, the first until 1986, the
second until 1993, the third until 2003 and the fourth until 2008.
The purpose of this paper is to review the articles on the anterior
cited aspects published since 2009, in order to complete the review
since our last publication [4]. The great interest of this technique can
be demonstrated from the increasing number of paper that appeared
in the literature since three decades ago, as can be seen in Fig. 2.
2. Theoretical and instrumental aspects
The determination of the analytical wavelength (the wavelength at
which the binary system is analyzed by DS) involves the analysis of the
derivative spectra. At the points where one of the components of the
mixture crosses the zero line, the value of the mixture derivative
should, according to the principle of the derivative additivity, be
equal to the derivative of the second component. However, this meth-
od, referred to as the zero-crossing technique, sometimes requires the
analysis of the spectrum at many wavelengths. This refers particularly
to the spectra with high course variation and high order derivative
spectra. Currently, the determination of the measuring points is easier
only in the ratio spectra derivative method, which does not make use
of the zero crossing technique for the reading of the derivative value.
In this way, Krystek [5] proposes two methods of preliminary selec-
tion of wavelengths which may meet the requirements for the
analytical wavelengths, whose proposed names are: “the method of
disturbing effect” and “the method of sixteen solutions.” They are
presented using, as example, 2,4-dichlorophenoxyacetic acid (2,4D),
2-(4-Chloro-2-methylphenoxy)propionic acid (MCPP), and 2-(2,4-
Dichlorophenoxy)propionic acid (2,4DP), which have very similar
but, at the same time, very complex spectra.
2.1. Method of disturbing effect
Derivative spectra were recorded for a series of solutions where
the concentration of one of the analyzed components is constant
1%
3%
6% 22%
12%
5%
inorganic
organic
pharmaceutical
51%
biological
food
environmental
other
Fig. 1. Application of DS in different areas.
Fig. 2. Evolution of DS publications from 1980 until today.
while the concentration of the other changes. The points at which
all the curves intersect are the points which may meet the require-
ments for the analytical wavelengths. The more distant they are
from the zero line, the more sensitive is the method at the given
wavelength. The points which are close to the zero line indicate low
sensitivity of the determination. The closer the intersection points of
the curves, the more precise the determination at these wavelengths.
2.2. Method of sixteen solutions
It involves preparation of a series of 16 solutions of two analyzed
components. In the series, each of the four concentrations of one
component corresponds with four different concentrations of the
other. The intersection points of the four curves representing the
same concentrations of one component and different concentrations
of the other may represent the analytical wavelengths for the first
component.
The combined use of DS and chemometric techniques has demon-
strated to be a highly convenient choice in the determination of mul-
ticomponent matrices presenting serious spectra overlapping, thanks
to their common potential ability to exploit minor spectral features.
In this sense, De Luca et al. [6] develop three multivariate procedures,
based on PCR, PLS1 and PLS2 algorithms that have been applied on
absorbance data of a ternary mixture of drugs. The main goal of the
work was a detailed comparison between the regression methods
when they are applied on ordinary or derivative spectral data. The in-
fluence of the derivative order from zero to four on the prediction
ability of the methods was investigated by the authors. Design of ex-
periments and calibration optimization was used as chemometric
tools to assist the development of the analytical methods. In this
work a suitable mixture design associated with response surface
methodology was defined, able to build a calibration set covering an
experimental domain which reflects the component combination in
the real samples. Validation of the models was performed by full
cross-validation procedure, providing to select the optimal number
of factors. In the optimization step, the wavelength regions con-
taining the most useful information were also selected and all the
useless signals, due to interferences or noise, were discarded. For
this aim, the authors developed a novel mathematical procedure,
based on the absolute values of the component regression coeffi-
cients. This procedure was compared with the other ones reported
in literature, by evaluating the application easiness and the improve-
ment of the predictive ability of the models. The optimized models
were compared by application to the analysis of synthetic mixtures
and commercial pharmaceutical formulations, in order to establish
their reliability in terms of accuracy and precision. According to
these studies, multivariate calibration methods (PCR, PLS-1, PLS-2)
coupled with derivative spectral data can be recommended as a
very suitable choice to resolve severe overlapped absorption spectra
of drug mixtures. This approach is simple in application, inexpensive,
 C. Bosch Ojeda, F. Sanchez Rojas / Microchemical Journal 106 (2013) 1–16
requires an easy treatment of the samples and provides reliable ana-
lytical results.
Fractional-order derivative spectroscopy has been developed by Li
and Hu [7] to resolve the overlapped Lorentzian peak-signals. Resolu-
tions are directly characterized by spectral parameters extracted from
the overlapped peak-signals. For this purpose, using the Haar wavelet
as a tool, the authors design a fractional-order differentiator to devel-
op the fractional-order derivative spectroscopy.
Wavelet transform (WT) has been rapidly developed during the
last decade in various branches, e.g. signal processing, de-noising,
spectral quantitative analysis, analysis of electrochemical noise data,
photo-acoustic signal processing, resolving simulated overlapped
spectra or flow-injection analysis. WT methods have been successful-
ly introduced into analytical chemistry applications and have
enriched the arsenal of chemometrics. WT has been established
with the Fourier transform as a data-processing method in analytical
chemistry. The main fields of application in analytical chemistry are
related to de-noising, compression, variable reduction, and signal
suppression.
Starting from 1989, this new mathematical technique has been
applied successfully for signal processing in chemistry. The number
of publications related to the application of WT to manipulate chem-
ical data has increased rapidly in the last years. WT was employed in
different fields of analytical chemistry that include flow injection
analysis, high performance liquid chromatography, infrared spec-
trometry, mass spectrometry, nuclear magnetic resonance spectrom-
etry, ultraviolet–visible spectrometry and voltammetry.
WT is a mathematical transformation for hierarchically decom-
posing functions. It led to a description of a function in terms of a
coarse overall shape and details of a graded sequence. In the spectral
studies, classical derivative and ratio spectra derivative methods were
used for the quantitative resolving of the mixtures containing two or
more compounds. Since the higher derivative process reduces the
peak amplitude, the process of finding zero-crossing points is very
difficult and the sensitivity of the method is decreasing. Particularly,
the ratio spectra derivative method leads us to an infinite value of
ratio spectra in some cases. For these reasons new methods should
be discovered and applied to the analytical problems [8–10]. In this
way, one promising method is WT, which was subjected to the opti-
mization problem in multi-component analysis. Wavelet analysis
was applied to removing non-constant, varying spectroscopic back-
ground in multivariate calibration. The importance of CWT comes
from the signal transformation of the original one to the other form
of signal giving opportunity of many families including Haar,
Daubechies and Mexican hat function to obtain the best calibration
signals. The selection of wavelet family is the most important step
to get the best signal transformation for a given mixture.
3. Applications
3.1. Inorganic analysis
DS is a very useful approach for determining the concentration of a
single component in mixtures with overlapping spectra as it may
eliminate interferences. So, DS has been used for the determination
of the individual analyte in complex matrices. Derivative methods
for the determination of metal ions through the formation of com-
plexes with diverse ligands are given in Table 1.
The research group of Devanna proposes the use of DS for the de-
termination of different metal ions using isonicotinoyl hydrazones in
which the interference zero-order method is eliminated in the first
order derivative methods [12–16,18,19].
On the other hand, DS is used for the simultaneous determination
of inorganic ions through the formation of their complexes with same
organic ligand. DS methods are used for the quantitative analysis of
binary mixtures because of its great sensitivity and selectivity as
3
well as a useful means of resolving two overlapping spectra and elim-
inating matrix interferences. Table 2 shows the analytical characteris-
tics of diverse derivative procedures for simultaneous determination
of binary mixtures of metal ions.
Very recently, a new method for the simultaneous determination
of Cu 2+, Zn 2+, Cd 2+, Hg 2+ and Pb 2+ is developed by Han et al. [31],
using mesotetra (3-methoxyl-4-hydroxylphenyl) porphyrin as re-
agent, by 2nd DS. By combining the spectrophotometer method and
PeakFit software, the authors solved the problem of simultaneous de-
termination of metal ion mixture, which was very difficult because of
the overlapping problem. In pH 10.35 (Borax–NaOH buffer), using the
previous cited reagent, micelle solution was formed after Tween-80
surfactant was added into the solution containing the five ions. The
original absorption spectrum of the above complexes was obtained
after heating in the boiling water for 25 min. The second-derivative
absorption peaks of five metal–porphyrin complexes can be separat-
ed from the original absorption spectrum by using chemometric
tool. The authors applied this method to determine the metal ions
of the soil, the edible fungus and the Chinese medicine cassia seeds.
The obtained results proved that this method is very simple and effec-
tive to simultaneous determination of metal ion mixture.
Finally, the UV 2nd DS of nitric oxide (NO) complexed with horse-
radish peroxidase, in an anaerobic phosphate buffer solution, is mea-
sured and a new method is proposed by Qiang and Zhou [32] using
second-order derivative spectral technique for the detection of NO
in serum samples.
3.2. Pharmaceutical analysis
In the last decades, DS has rapidly gained application in the field of
pharmaceutical analysis to overcome the problem of interference,
due to the substances other than analytes, commonly present in phar-
maceutical formulations or for combination of two or more drug sub-
stances. DS has been successfully used as a quality control tool in
pharmaceutical analysis for the simultaneous determination of
drugs in multi-component formulations. This technique, accessible
to most laboratories, offers an alternative means of enhancing the
sensitivity and specificity in mixture analysis. The procedure is sim-
ple, rapid and does not require any preliminary separations or treat-
ment of the samples.
The analytical characteristics of DS methods for individual drugs
determination are described in Table 3.
During the last few decades, a great interest has been seen in the
development of various novel drug delivery systems. In many of
these formulations, surfactants like polysorbates (Tweens) and co-
surfactants like propylene glycol and polyethylene glycol (PEG) are
used. However, as those additives exhibit considerable absorbance
at the wavelength of maximum absorbance of diazepam UV-
spectrometry method cannot be used to estimate the drug accurately
in their presence. In this sense, Dastidar and Sa [38] present 1st DS as
an accurate, precise, and simple method in comparison to conven-
tional UV-spectrophotometry method for the estimation of diazepam
in presence of Tween-20 and propylene glycol.
UV–vis spectrophotometry represents a suitable method for the
routine analysis of active ingredients in raw materials, since it is
fast, easy to perform and does not require expensive instruments. Be-
cause its use is limited to the analysis of substances able to absorb
light on the UV–vis domain, spectrophotometry is not useful for the
direct determination of aminoglycosidic antibiotics, substances with
weak light-absorbing capacity. Although the lack of chromophores
in the chemical structure of aminoglycosides makes direct detection
and quantification impossible, indirect spectrophotometry can be
used in their case.
Table 4 illustrates the analytical characteristics of numerous deriv-
ative methods for simultaneous determination of drugs.
4 C. Bosch Ojeda, F. Sanchez Rojas / Microchemical Journal 106 (2013) 1–16

Two simple and rapid spectrophotometric methods were devel-

[11]

[12]
[13]

[14]

[15]
[16]

[17]
[18]

[19]

[20]
Ref.
oped by Belal et al. [87] for the resolution and analysis of the binary

Synthetic samples of alloy and river waters

mixture of glyburide (GB) and metformin HCl (MF) in tablets. The

Synthetic samples of alloy and river water

Synthetic mixtures and Algerian low gold

Foodstuffs, pharmaceutical samples and

first method, zero-crossing first derivative spectrophotometry, de-

Water, biological and pharmaceutical

pends on measuring the first derivative values at 314.7 nm for GB

Environmental samples and alloys

and 228.6 nm for MF. The second method, ratio first derivative spec-
trophotometry, depends on measuring the amplitudes of the first de-

Rock and synthetic samples

rivative of the ratio spectra at 314.7 nm for GB and 238.0 nm for MF.
Synthetic alloy samples

The proposed methods were applied successfully to the assay of these

drugs in commercial tablets. The zero-crossing derivative spectropho-

Portland cement
tometry is more rapid and simple than ratio derivative spectropho-
ore solutions
Applications

tometry; however the ratio derivative spectrophotometry has

samples

samples
greater sensitivity and accuracy. These proposed methods could be
Alloys
alloys

regarded as useful alternative to the reported chromatographic and

electrophoretic techniques in the routine quality control of pharma-
0.004

ceutical formulations, allowing qualitative and quantitative informa-

0.96

0.13
RSD
(%)

0.7
b3

–
–

tion to be simultaneously and rapidly achieved with a relatively

-

inexpensive instrumentation.
There are some methods described in the literature to the resolu-
0.1635–1.635
Linear range

0.857–5.142

0.414–10.36
0.095–0.863

Up to 12.26

tion of three components. So, two spectrophotometric methods are

0.294–2.94

0.202–4.04
0.505–6.06
(μg mL− 1)

1.19–11.9

0.02–0.6

described by Abdel-Hay et al. [106] for the resolution of the three-

component mixture of amiloride hydrochloride (AMD), hydrochloro-
thiazide (HCT) and timolol maleate (TIM). The first method involves
presence of zinc; salting-out method using sodium chloride to cause phase separation

Direct and 1st deriv.; zero-crossing method; HClO4 medium; 662.5 nm; simultaneous

the use of DS with the zero-crossing technique where AMD was deter-
mined using its 0D and 1D amplitudes at 365 and 385 nm, respectively,
1st and 2nd deriv.; pH 3; 433 and 457 nm, resp. without heating or extraction;

while HCT and TIM were determined by measuring the 3D amplitude at

1st deriv.; zero-crossing method; 445 nm; selective extraction of gold in the

265 nm and the 1D amplitude at 315.4 nm, respectively. The second

Direct and 1st deriv.; peak-zero method; pH 3.5; 473 and 540 nm, resp.

method involves the application of the ratio-spectra zero-crossing

determination of U(VI) and Zr(IV) in mixed aqueous organic medium
1st and 2nd deriv.; peak height method; pH 4; 436 and 441 nm, resp.

first and second derivative spectrophotometry where two points have

1st deriv.; ratio spectrum zero-crossing method; pH 9.5; 622 nm

been used for the quantification of each compound. For the determina-
tion of AMD, HCT was used as a divisor and the 1DD and 2DD values at
299.4 and 311 nm, respectively, were plotted against AMD concentra-
Direct and 1st deriv.; peak zero method; pH 9; 440 nm

tion; while – by using TIM as divisor – the 2DD amplitudes at 264.2

and 290 nm were found to be proportional to HCT concentration. TIM
1st deriv.; peak height method; pH 4.5; 346 nm
1st deriv.; peak height method; pH 10; 448 nm

was assayed in the mixture using its 1DD amplitudes at 289.8 nm

more sensitive than the zero order method

(Divisor was AMD) and 314.8 nm (Divisor was HCT).

Two UV spectrophotometric methods have been developed by
Pathak and Rajput [107] based on the first derivative spectrophotom-
etry for simultaneous estimation of doxylamine succinate, pyridoxine
hydrochloride, and folic acid in tablet formulations. In method 1, the
Analytical characteristic of derivative procedures for individual determination of metal ions.

concentrations of these drugs were determined by using linear re-

gression equation. Method 2 is also based on first derivative spectro-
photometry however simultaneous equations (Vierdot's method)
were derived on derivative spectra. The first derivative amplitudes
pH 3; 402 nm

at 270.0, 332.8 and 309.2 nm were utilized for simultaneous estima-

Remarks

tion of these drugs respectively by both methods. In both methods,

linearity was obtained in the concentration range 2.5–50, 1–40 and
1–30 μg mL − 1 for doxylamine succinate, pyridoxine hydrochloride,
2-hydroxy-3-methoxy-benzaldehyde-isonicotinoyl-
Cinnamaldehyde-4-hydroxy-benzoylhydrazone in

and folic acid respectively.

Diacetylmonoxime-4-hydroxybenzoylhydrazone

Two spectrophotometric methods that do not require prior sepa-

Diacetyl-monoxime isonicotinoyl-hydrazone

ration for simultaneous estimation of three drugs: paracetamol,

3,5-Dimethoxy-4-hydroxy-benzaldehyde-

3,5-dimethoxy-4-hydroxy-benzaldehyde-
Dithizone in presence of cetylpyridinium

Cinnamaldehyde isonicotinoylhydrazone

nimesulide, and tizanidine in tablet formulation have been reported

by Chandratrey and Sharma [108]. Method 1 was based on DS and
the absorbances were measured at 229.5, 271, and 323.0 nm, being
neutral surfactant Triton X-100

the zero crossing points for paracetamol, nimesulide and tizanidine,

respectively. Method 2 is based on multi-wavelength spectroscopic
isonicotinoyl-hydrazone

isonicotinoyl-hydrazone
chloride as surfactant

method, absorbances of standard solutions were measured at

Alizarin complexone

229.0 nm, 272.0 nm, 262.0 nm and 323.0 nm based on the statistical
calculations and results of the sample solutions.
Arsenazo-III
hydrazone

First and second order DS methods with an application of base line

Elements Reagents

to peak technique were used by Stolarczyk et al. [109] for the deter-
mination of active pharmaceutical ingredients at two wavelengths:
fluphenazine (D1 at λ = 251 nm and λ = 265 nm, D2 at λ = 246 nm
and λ = 269 nm), pernazine (D1 at λ = 246 nm and λ = 258 nm, D2
Table 1

at λ = 254 nm and λ = 262 nm), haloperidol (D1 at λ = 235 nm and

Mo
Au

Ru
Ru

Zn
Pb

Ni

Zr
Sr
U

λ = 253 nm, D2 at λ = 230 nm and λ = 246 nm), and promazine

 C. Bosch Ojeda, F. Sanchez Rojas / Microchemical Journal 106 (2013) 1–16 5

(D1 at λ = 246 nm and λ = 251 nm, D2 at λ = 255 nm and

[21]

[22]

[23]

[24]

[25]

[25]

Synthetic mixtures and commercial pharmaceutical [26]

[27]

[28]

[29]

[30]
Ref. λ = 262 nm). Linear dependence of derivative values on analyte con-
centration is maintained in a range 3.12–44.80 μg mL − 1.

Ferro-vanadium alloy, phosphor bronze, rice and

Ferro-vanadium alloy, phosphor bronze, rice and

Pd in hydrogenation catalyst and W in industrial

Pd in hydrogenation catalysts and Ru in water
3.3. Stability-indicating methods
Synthetic binary mixtures and real samples
A stability indicating method is a quantitative test method that
can detect possible degradants with time and impurities of drug sub-
Human hair and serum samples stance and drug products, normally using HPLC. Information of type
and amount of degradation products over time is important for safe-
ty of drugs.

waste water samples

DS was used for the stability-indicating determination of diverse

and real samples

drugs [110–124]. DS is a useful tool in the quantification of mixture
Applications

of drugs. It could be even used as a stability-indicating technique

preparation
groundnut

groundnut

Synthetic
for the analysis of drugs in presence of their degradation products,

samples
Alloys

Alloys

Alloy
by solving the problem of the overlapping absorption bands.
The photodegradation behavior of barnidipine (BAR) under
stressing light and natural light was evaluated and the relative deg-
RSD (%)

b1.5 for

0.15 for

radation pathways and kinetics under these irradiation conditions

both

both
0.43
0.67

0.15
0.39

b4

were compared by Ioele et al. [110]. BAR photodegradation was

–

–
monitored by HPLC and zero-crossing DS. Adoption of the spectro-
2–12 for both

1–30 for both

Linear range

photometric analysis was justified by the authors due to easy record-

0.558–3.348
0.24–2.4 for

0.635–3.81

0.635–3.81
0.509–3.06

0.21–12.78
0.25–13.42

0.92–11.40
(μg mL− 1)

0.53–6.40

ing of the spectra and the rapid interpretation of the data, which
1.3–5.4

0.1–2.5
1.1-8.3

0.1–10
0.1–11
0.5–6

makes this technique very attractive for routine uses. On the other
both

hand, zero-crossing is a powerful technique for the quantitative

–

assay of the components of a mixture, particularly effective when a

wide peak overlapping is present in the corresponding zero-order
spectrum.
4th deriv. by zero crossing method and H-point standard addition method; pH 4; 440
2nd deriv.; zero-crossing method; pH 5.5; 380 nm for Cu and 400 nm for V; blue and

1st deriv.; zero crossing method at 388 and 487 nm for Fe in presence of Cu and 367

Spectrophotometric studies of the degradation of biapenem were

Direct and 1st deriv.; in bis-2-ethyl hexyl sulfosiiccinate micellar solution; pH 2.5;

and 414 nm for Cu in presence of Fe; derivative ratio spectra method at 492 and

and 465 nm for Cu and 350 and 365 nm for Pd; complexation in micellar media
1st deriv.; zero-crossing method and H-point standard addition method; pH 6;

conducted by Cielecka-Piontek et al. [111] in order to develop a sim-

3rd deriv.; zero crossing method; basic media and extracted with chloroform;
2nd deriv.; zero-crossing method; pH 6.5; 387.2 nm for Cu and 440 nm for Fe

ple and fast analytical method, for quantification of biapenem in the

presence of its degradation products. The method was based on the
Direct and 2nd deriv.; peak-zero method; pH 6; 455 and 424 nm, resp.

measurement of first-derivative amplitudes at zero crossing point

(λ = 312 nm) and the peak-to-zero technique.
1st deriv.; zero-crossing method; pH 2; 422 and 426 nm, resp.

Al-Arfaj et al. [112] describe a second DS method (at 291.2 nm

which was the zero crossing point of candesartan in methanol) for
cetyltrimethylammonium bromide as surfactant at 25 º C
Analytical characteristics of derivative procedures for simultaneous determination of mixtures of metal ions.

the determination of candesartan cilexetil in the presence of its alka-

558 and 580 nm for Cu and 600 and 630 nm for iron

2-hydroxy-3-methoxy benzaldehyde 2nd deriv.; pH 3; 445 nm for Pd and 385 nm for Ru

2nd deriv.; pH 5; 362 nm for Pd and 374 nm for W

yellowish-green and blue complexes for Fe and Cu

line degradation product, candesartan.

Four sensitive, selective and precise stability-indicating methods
for the determination of clopidogrel bisulfate (CLP) in the presence
503 nm for Fe and 383 and 419 nm for Cu

of its alkaline degradate and in pharmaceutical formulations were

developed and validated by Zaazaa et al. [113]. Method A is a second
472 nm for Cu and 501 nm for Ni

derivative spectrophotometric, which allows the determination of

yellow complexes for Cu and V

CLP in presence of its alkaline degradate at 219.6, 270.6, 274.2 and

278.4 nm (corresponding to zero-crossing of degradate). Method B
is the first derivative of the ratio spectra spectrophotometric method,
by measuring the peak amplitude at 217.6 and 229.4 nm using aceto-
nitrile. Method C based on the determination of CLP by the bivariate
calibration depending on simple mathematic algorithm which pro-
Remarks

vides simplicity and rapidity; the method depends on quantitative

evaluation of the absorbance at 210 and 225 nm. Method D is a
TLC-densitometric, where CLP was separated from its degradate on
silica gel plates using hexane:methanol:ethyl acetate (8.7:1:0.3,
4-phenylpiperazine-carbodithioate
6-(2-naphthyl)-2,3-dihydro-1,2,4-

v/v/v). This method depends on the quantitative densitometric eval-

2-acetylpyridine-4-methyl-3-

3,4-dihydroxy-benzaldehyde
1-(2-pyridylazo)-2-naphthol

uation of thin layer chromatogram of CLP at 248 nm. A and B spectro-

4-(2-pyridylazo) resorcinol

photometric methods are well-established techniques that are able

isonicotinoylhydrazone

to enhance the resolution of overlapping bands. These methods are

8-hydroxyquinoline
thiosemicarbazone

thiosemicarbazone

thiosemicarbazone

thiosemicarbazone
2-ketobutyric acid

2-ketobutyric acid

simple, more convenient, less time consuming and economic stabili-

triazine-3-thione
Alizarin yellow

ty indicating methods compared to other published LC methods. Ki-

netic studies of the decomposition of drugs using stability testing
Elements Reagents

techniques are essential for the quality control of such products. In

this work, the authors present a kinetic investigation of alkaline deg-
radation of CLP. Bivariate calibration method provided simple and
rapid determination of CLP with minimal sample and data manipula-
Table 2

Ru
Pd

W
Fe

Fe

Ni

Fe

Fe

Fe

Ni

tion. Finally, the advantages of TLC-densitometric method are that

V
Cu

Cu

Cu

Cu

Cu

Cu
Co

Co

Pd

Pd
Al

several samples can be run simultaneously using a small quantity

 6
Table 3
Analytical characteristics of derivative procedures for individual determination of pharmaceutical compounds.

Compound Remarks Linear range (μg mL− 1) Precision (%) Ref.

Atenolol Zero (276 nm), 1st (273, 276 and 285 nm), 2nd (276, 279, 282 and 287 nm) and 3rd 2.5–17.5 b6.04 [33]
(275, 278 and 281 nm) deriv.
Cabergoline Zero (280 nm) and 2nd deriv. (227–232 nm) 1–125 b1.10 [34]
Candesartan cilexetil 1st deriv. (270.1 nm); in methanol with 0.35% polysorbate 20 at pH 6.5 phosphate 6–32 b2 [35]

C. Bosch Ojeda, F. Sanchez Rojas / Microchemical Journal 106 (2013) 1–16

buffer (1:9) solutions
Cefetamet pivoxil hydrochloride Colorimetric using folin ciocalteau reagent and 1st deriv. – – [36]
Cefuroxime axetil Zero in HCl 0.1 M (281 nm) and 1st deriv. in NaOH 0.1 M (difference between maxima 4–30 – [37]
at 266 nm and minima at 300 nm)
Diazepam 1st deriv. (260 nm); pH 7.4 1–9 b1 [38]
Drotaverine hydrochloride 2nd deriv. (247.4 nm) 4–32 – [39]
Fluconazole 1st deriv. (268 nm); Three methods of analysis (bioassay, first order derivative UV 150–350 0.65 [40]
spectrophotometry and chromatographic methods); All methods showed to be specific,
precise, accurate and linear in the concentration ranges tested. In both raw material and capsules
Gemifloxacin mesylate Zero (430 nm), 1st (480 nm) and 2nd (500 nm) deriv.; by chelation with Pd(II); used as a 2–14, 1–10 and 1–15, resp. 0.1530, 0.0177 and 0.0138, resp. [41]
catalyst in the preparation of wide range of drugs, essentially present in biological fluids
Gemifloxacin mesylate Zero (545 nm), 1st (620 nm) and 2nd (660 nm) deriv.; by chelation with Cr(III) ion 2–20, 1–15 and 1–25, resp. 0.1463, 0.0106 and 0.0159, resp. [42]
Gentamicin sulfate 3rd deriv. (281 nm); after modifying the molecule with o-phthalaldehyde. It was found that for 0.004–0.008 (%) 2.52 [43]
the selected wavelength of 281 nm, the value of the third derivative depends on the analyte
concentration and shows no interference with coexisting constituents.
Letrozole Zero (240 nm), 1st (224 nm), 2nd (241 nm) and area under curve method (235–245 nm) 0.25–20 b1 in all cases [44]
Losartan potassium Zero (205 nm) and 1st (234 nm) deriv. 3–7; 6–14 0.95 [45]
Nebivolol hydrochloride 2nd (296 nm) and 3rd (290 nm) deriv. 40–80; 10–60 – [46]
Neomycin 1st (277 nm) deriv. Indirect DS method based on the capacity of neomycin to form in the presence of 0.102–0.51 1.9 [47]
Cu2+ ions complex combinations with increased UV–vis light absorbing capacity. Optimum complex
formation was found to take place in the presence of CuCl2.6H2O 1 mg mL− 1 when 20% methanol in
bidistilled water was used as solvent.
Oxazepam Zero (228.4 nm), 1st (306–330.2 nm), 2nd (321.2 nm), 3rd (270.4), 3rd (270.4–291 nm) and HPTLC UV 0.5–25 b5 in all cases [48]
ensitometry
Pioglitazone Zero (270.2 nm), 2nd (272–287.4 nm) deriv. and colorimetric method by ion par 5–20; 2–12; 20–100 b4 in all cases [49]
Racecadotril Zero (231 nm), 2nd (250 nm) and 3rd (240 nm) deriv. 8–100 – [50]
Ranitidine hydrochloride Zero (312 nm), 1st (332 nm) deriv. 0.5–35.1 – [51]
Ritonavir 2nd deriv. (222.3 nm) 10–30 b2 [52]
Tenofovir Zero (260 nm) and 1st (273 nm) deriv. 5–40 2 [53]
[54]
Tramadol hydrochloride Zero, 1st and 2nd deriv. (240–290 nm) 10–100 – [55]
Triclosan 1st deriv. 7.5–45 – [56]
 C. Bosch Ojeda, F. Sanchez Rojas / Microchemical Journal 106 (2013) 1–16
of mobile phase unlike HPLC, thus lowering analysis time and cost per
analysis and provide high sensitivity and selectivity.
Three methods for the determination of diacerein (DIA) in the
presence of its alkaline degradation product were developed by
Nebsen et al. [114]. Method A is a first DS at 322 nm, corresponding
to zero crossing of degradate. Method B is a first derivative of the
ratio spectra by measuring the peak amplitude at 352 nm. Method C
is a TLC-densitometric, where DIA was separated from its de-
gradate on silica gel plates using ethyl acetate:methanol:chloroform
(8:1.5:0.5). This method depends on quantitative densitometric eval-
uation of thin layer chromatogram of DIA at 340 nm.
Cielecka-Piontek and Jelinska [115] develop a spectrophotometric
method of determination of doripenem in pure form and during deg-
radation in the presence of opened β-lactam ring and dimeric prod-
ucts. The first-derivative with or without the substration technique,
depending on formed products degradation was applied at 295 and
324 nm.
Stability-indicative determination of ertapenem (ERTM) in the
presence of its β-lactam open-ring degradation product, which is
also the metabolite, was investigated by Hassan et al. [116]. The stud-
ied methods include first derivative, first derivative of the ratio spec-
tra and bivariate analysis. Method A by applying the first derivative
ultraviolet spectrophotometry; the method can solve the problem of
spectral bands overlapping between ERTM and its degradant without
sample pretreatment or extra separation steps. When the first-
derivative spectra were examined, it was found that ERTM could be
determined at 316 nm, where it's degradant has no contribution
(zero crossing) allowing accurate determination of ERTM in presence
of its degradant. Method B was derivative-ratio spectroscopy, a useful
tool in quantification of drugs. It could be applied as a stability-
indicating method for the determination of ERTM in presence of its
degradant. It could determine ERTM in the presence of higher degra-
dation percentage than the first derivative method does. Linear cali-
bration graphs were obtained for ERTM in concentration range of
4–60 μg mL − 1 by recording the peak amplitudes at 298 and 316 nm
using 28 μg mL − 1 of the degradant as a divisor. Method C: For the bi-
variate determination of ERTM and its degradant, the wavelengths
215 and 297 nm were used. The bivariate calibration method may
be competitive and in some cases even superior to commonly use
DS methods as applied for the resolution of binary mixtures. The ad-
vantage of bivariate calibration method is its simplicity and the fact
that derivatization procedures are not necessary. Unlike other
chemometric techniques, there is no need for full spectrum informa-
tion and no data processing is required.
Reversed phase-high performance liquid chromatography (RP-
HPLC), thin layer chromatography (TLC) densitometry and first deriv-
ative spectrophotometry techniques are developed and validated by
El-Moghazy et al. [117] as a stability-indicating assay of ezetimibe
in the presence of alkaline induced degradation products. RP-HPLC
method involves an isocratic elution on a Phenomenex Luna 5 μ C18
column using acetonitrile:water:glacial acetic acid (50:50:0.1 v/v/v)
as a mobile phase at 235 nm. TLC densitometric method is based on
the difference in Rƒ-values between the intact drug and its degrada-
tion products on aluminum-packed silica gel 60 F254 TLC plates as sta-
tionary phase with isopropanol:ammonia 33% (9:1 v/v) as a
developing mobile phase. On the fluorescent plates, the spots were
located by fluorescence quenching and the densitometric analysis
was carried out at 250 nm. DS, the zero-crossing method, ezetimibe
was determined using first derivative at 261 nm in the presence of
its degradation products. The three methods could be easily per-
formed for the analysis of ezetimibe in raw material and in pharma-
ceutical dosage forms without the interference of tablet excipients
and their impurities, which makes them suitable for quality control
analysis.
Five methods were presented by Lotfy et al. [118] for the determina-
tion of famciclovir (FCV) in the presence of its alkaline-induced
7
degradation product. Method A uses first DS at 321 nm. Method B was
the first derivative of the ratio spectra at 256 nm. Method C was based
on the reaction of FCV with hydroxylamine to form hydroxamic acid
that reacts with Fe3+ to form ferric hydroxamate that was measured
at 503 nm. Method D was based on the separation of FCV from its degra-
dation product on silica gel 60 F254, using chloroform:methanol (70:30)
followed by densitometric measurement at 304 nm. Method E was
based on a HPLC separation using an ODS column with a mobile phase
of methanol: 50 mM dipotassium hydrogen phosphate (25:75, pH 3)
at 304 nm.
Markovic et al. [119] investigate the application of DS for the anal-
ysis of 2-phenoxypropionate ester of fluocinolone acetonide (FA-21-
PhP) solvolysis in ethanol/water solution using sodium hydrogen car-
bonate. method was used by the authors as a referent method. Due to
the structural similarity of the solvolyte ethyl 2-phenoxypropionate
(EtPhP) to the parent FA-21-PhP, particular consideration was paid
to the selection of derivative order for efficient spectra resolution in
solvolysis of ternary mixture. The application of zero-crossing tech-
nique in second-order derivative spectrophotometry was possible at
only one analytical wavelength (274.96 nm) which was the joint
zero-crossing point of parent ester and solvolyte EtPhP. The second-
order derivative assay of fluocinolone acetonide (FA) has a limitation
in the initial stage of solvolysis due to lower sensitivity caused by
means of FA amplitude satellite peak. It could be expected that DS
in fourth-order spectra would be more efficient for in vivo analysis
using esterases due to more substantial difference in zero-crossing
points of parent ester and corresponding acid (PhPA). In this way
FA is suppressed (binary mixture) and the sensitivity for parent
ester assay would be higher due to central peak amplitude measure-
ments. The HPLC method was used as a referent method and the peak
area of parent ester (FA-21-PhP) was the signal for monitoring solvo-
lytic reaction. Percentages of solvolysed FA-21-PhP, as well as the sol-
volytic rate constants, obtained by DS and HPLC confirmed that
simple and fast DS method could be used as an alternative assay to
HPLC method.
Three stability-indicating methods were developed by Mohamed
et al. [120] for the determination of racecadotril (RCT) in the presence
of its alkaline degradation products. Method A was an HPLC method
in which efficient chromatographic separation was achieved on
a C18 analytical column and on a mobile phase of acetonitrile–
methanol–water–acetic acid (52:28:20:0.1, v/v/v/v). Method B was
a densitometric evaluation of thin-layer chromatograms of the drug
using a mobile phase of isopropanol–ammonia (33%)-n-hexane
(9:0.5:20, v/v/v); the chromatograms were scanned at 232 nm. Meth-
od C was based on the use of first DS at 240 nm.
Three stability-indicating assay methods were developed by
Abdel-Fattah et al. [121] for the determination of tropisetron in a
pharmaceutical dosage form in the presence of its degradation prod-
ucts. The proposed techniques are HPLC, TLC, and first-DS. Acid degra-
dation was carried out, and the degradation products were separated
by TLC and were identified by IR, NMR, and MS techniques. The HPLC
method was based on the determination of tropisetron in the pres-
ence of its acid-induced degradation product on an RP Nucleosil C18
column using methanol:water:acetonitrile:trimethylamine (65:20:
15:0.2, v/v/v/v) mobile phase at 285 nm. The TLC method was based
on the separation of tropisetron and its acid-induced degradation
products, followed by densitometric measurement of the intact spot
at 285 nm. The separation was carried out on silica gel 60 F254 alumi-
num sheets using methanol:glacial acetic acid (22:3, v/v) mobile
phase. DS method was based on the measurement of first-derivative
amplitudes of tropisetron in H2O at the zero-crossing point of its
acid-induced degradation product at 271.9 nm.
A second DS method and a derivative ratio spectrum zero crossing
method were used to determine raubasine and almitrine dismesylate
in the presence of raubasine degradation product, using methanol as
a solvent [122].
 8
Table 4
Analytical characteristics of derivative procedures for simultaneous determination of pharmaceutical compounds.

Compounds Remarks Linear ranges Ref.

Aceclofenac Amplitude in 1st deriv. of the ratio spectra at 256 and 268 nm – [57]
Paracetamol
Aceclofenac 1st deriv. by zero crossing method, at 250 and 313 nm 2–20 and 1–10 μg mL− 1 [58]
Tizanidine
−1
Acetaminophen Ascorbic acid Zero and derivative data (215–310 nm) using PCR and PLS chemometric methods 1.5–24.2 and 1.8–21.1 μg mL [59]
1 × 10− 5–6 × 10− 4 and 1 × 10− 5–10 × 10− 5 M

C. Bosch Ojeda, F. Sanchez Rojas / Microchemical Journal 106 (2013) 1–16

Acetaminophen Tramadol 2nd deriv. by zero crossing method, at 308 and 285.7 nm [60]
Albendazole 2nd deriv. at 327.5 and 223.2 nm and PCR, PLS, CLS chemometric methods of drugs dissolved in 2 × 10− 6–3.5 × 10− 5 M for both drugs [61]
Praziquantel methanol–HCl solution
Almitrine dismesylate 1st deriv. for raubasine and 1st deriv. ratio spectra for almitrine using methanol as solvent 10–24 and 6–20 μg mL− 1 [62]
Raubasine
−1
Amitriptyline 1st deriv. at 219 and 230 nm, reversed phase HPLC and HPTLC 1–20 and 2–24 μg mL for DS [63]
Chlordiazepoxide
−1
Amoxicillin Zero (absorbance ratio and compensation), 1st deriv. and 1st deriv. ratio spectra 100–160 and 10–35 μg mL [64]
Clavulanate
Amoxicillin Zero (absorbance ratio and compensation), 1st deriv. ratio spectra and reversed phase HPLC 60–140 μg mL− 1 for both drugs [65]
Cloxacillin
Amoxicillin 1st deriv. at 334 nm for ranitidine, bivariate calibration algorithm (at 190 and 226 nm) and Vierortd method 2 × 10− 6–2 × 10− 5 and 4 × 10− 6–6 × 10− 5 M [66]
Ranitidine (at 208 and 312 nm)
Antazoline 1st deriv. ratio spectra at 235 and 227.2 nm 10–150 μM [67]
Naphazoline
Atorvastatin calcium 1st deriv. ratio spectra at 266.6 and 262.2 nm and reverse phase HPLC 3–15 μg mL− 1 for both drugs and for both techniques [68]
Ezetimib
Benzoic acid 1st deriv. by zero crossing method, at 283 and 310 nm and reverse phase HPLC 10–30 and 20–60 μg mL− 1 [69]
Salicylic acid
−1
Brucine 1st deriv. at 256.4 and 265.4 nm 10–50 μg mL for both drugs [70]
Strychnine
−1
Caffeine 2nd deriv. by zero crossing method, at 288 and 260 nm 0.1–20 and 0.1–30 μg mL [71]
Paracetamol
Carvedilol 1st deriv. at 248 and 285 nm 0.05–1.5 and 0.5–15 μg mL− 1 [72]
Hydrochlorothiazide
Cetrizine 2nd deriv. at 238.08 nm and 271.39 nm and dual wavelength; in marketed brands of tablet 10–60 and 200–700 μg mL− 1 [73]
Phenylpropanolamine
−1
Chlordiazepoxide 1st deriv. at 219 and 231.5 nm 2–24 and 1–20 μg mL [74]
Imipramine
Chlorhexidine 1st deriv. at 290 nm and 2nd deriv. at 272 and 276 nm (peak to peak amplitude) PLS 5–9 and 160–480 μg mL− 1 [75]
Lidocaine
Chlorphenamine maleate 1st deriv. at 274 and 312 nm; CLS, PLS, PCR. The detection limit for PLS and PCR were slightly higher than for 1st deriv. 8 × 10− 7–3 × 10− 4 and 1.8 × 10− 6–3 × 10− 4 M [76]
Dibucaine because 1st deriv. is zero order (from a chemometric view) and does not incorporate noise into the measurement,
while the multivariate calibration methods consider the spectral ranges that do not have only analytic information since
the noise has not been totally eliminated.
Ciprofloxacin 301.5 nm (zero crossing for ciprofloxacin) and 263 nm (zero crossing for ornidazole) 0–40 and 0–60 μg mL− 1 [77]
Ornidazole
Cyproterone acetate 3rd deriv. at 316 and 226 nm and CWT. High amplitude in CWT method improves the sensitivity and having several 5–60 and 1–8 μg mL− 1 [78]
Ethinyl estradiol zero cross-points can be used to eliminate probable interferences and diminishing the noise.
Desloratadine 1st deriv. at 280 and 244 nm 2.5–15 and 120–720 μg mL− 1 [79]
Pseudoephedrine
Diflucortolone valerate Liquid chromatographic and two spectrophotometric methods, principal component regression and 2.4–40 and 60–260 μg mL− 1 [80]
Isoconazole nitrate 1st deriv. at 247.8 and 240.2 nm
Domperidone Ratio spectra DS at 271.5 and 249 nm and direct spectrophotometry using simultaneous equation – [81]
Rabeprazole method at 287 and 258 nm
−1
Domperidone 1st deriv. at 253.2 and 266.4 nm 9–45 and 6–30 μg mL [82]
Rabeprazole
−1
2-Ethylhexyl-4-methoxycinnamate 2nd deriv. 50–1000 μg mL [83]
Oxybenzone
Ezetimibe 1st deriv. at 223.4 and 237.4 nm 2.5–15 μg mL− 1 for both drugs [84]
Rosuvastatin
Ezetimibe 1st deriv. at 237.6 and 248 nm 4–24 and 2–24 μg mL− 1 [85]
Simvastatin
−1
Ezetimibe 1st deriv. at 265 and 219 nm 1–20 and 2–40 μg mL [86]
Simvastatin
Glyburide Two 1st deriv. methods; in tablets 10–125 and 2–18 μg mL− 1 [87]
Metformin (zero-crossing and ratio first derivative spectrophotometry)
Guaifenesin 1st deriv. at 282.0–290.2 and 277.4–287.8 nm; in liquid or solid dosage forms; combination of H-point standard – [88]
Theophylline addition methods and DS

C. Bosch Ojeda, F. Sanchez Rojas / Microchemical Journal 106 (2013) 1–16

−5 −5
Hydrochlorothiazide 1st deriv. at 332 and 244.6 nm 1 × 10 –5 × 10 M [89]
Losartan
−1
Hydrochlorothiazide 1st deriv. at 334.6 and 294.6 nm 10–60 and 8–40 μg mL [90]
Nebivolol
Hydrochlorothiazide 1st deriv. by ratio spectra at 231.0 and 271.0 nm and zero crossing techniques at 257.8 and 240.2 nm 0.5–15 and 0.8–24 μg mL− 1 [91]
Olmesartan medoxomil
Hydrochlorothiazide 1st derive. at 233 and 243 nm. 2nd deriv. at 231 nm and 224 nm 1–6 and 0.75–5 μg mL− 1 [92]
Triamterene
−1
Hypophyllanthin 1st deriv. at 252.4 and 259.2 nm 4–20 and 10–50 μg mL [93]
Phyllanthin
Imidacloprid 1st deriv. at 249 and 236 nm; in commercial formulations of imidacloprid, good agreement with the comparative 1.6–22.5 μg mL− 1 for both drugs [94]
6-chloronicotinic acid HPLC–DAD procedure
Itopride 1st deriv. at 288 and 238.5 nm 5–40 and 3–15 μg mL− 1 [95]
Pantoprazole
−1
Levocetirizine 1st deriv. at 238.2 and 291.6 nm 5–30 and 10–60 μg mL [96]
Montelukast
−1
Levofloxacin 1st deriv. at 277.5 and 319 nm 10–50 and 20–80 μg mL [97]
Ornidazole
Lovastatin 2nd deriv. at 237.7 and 233.2 nm 1.508 × 10− 6–15.08 × 10− 6 and 1.02 × 10− 6–10.2 × 10− 6 [98]
Simvastatin
Mefenamic acid Zero, 1st and 2nd deriv. using peak-peak and peak-zero measurements 14–24 and 4–14 μg mL− 1 [99]
Meloxicam
−1
Metformin Three spectrophotometric methods and one HPLC method; in tablets 1–10 and 5–50 μg mL [100]
Rosiglitazone maleate
Metronidazole Three spectrophotometric methods (1st deriv at 218.3 nm, 245.6 nm); pure form and in pharmaceutical formulations; mean 5–25 μg mL− 1 for both drugs [101]
Spiramycin centring of the ratio spectra, allows the determination of both MZ and SP.
Ofloxacin 1st deriv. at 295 and 305 nm – [102]
Tinidazole
−6 −4 −5 −3
Oxolinic acid 1st deriv. at 266.8 and 382.2 nm; pH 7 for OTC; acetonitrile for OA extraction 2.43 × 10 − 0.8 × 10 and 1.88 × 10 − 0.1 × 10 M [103]
Oxytetracycline
−1
Phenylephrine Three UV spectrophotometric methods: zero crossing derivative spectrophotometry at 284.0 nm for PHE and 241.2 nm for 25–125 and 4–20 μg mL [104]
Tropicamide TPC, dual wavelength method at 260.8 nm and 268.2 nm for estimation of PHE and 245.4 nm and 271.8 nm for TPC and
ratio spectra DS using amplitudes at 270.8 nm for PHE and 240.8 nm for TPC .
Sulfamethoxazole 1st deriv. at 256 and 293 nm 5–150 μM [105]
Trimethoprin

9
10 C. Bosch Ojeda, F. Sanchez Rojas / Microchemical Journal 106 (2013) 1–16
Four sensitive, selective and precise stability indicating methods
for the determination of isopropamide iodide (ISO) and trifluopera-
zine hydrochloride (TPZ) in their binary mixture and in presence of
trifluoperazine oxidative degradate (OXD) were developed by Abbas
et al. [123]. Method A is a DS, where ISO was determined by the
first derivative at 226.4 nm while TPZ was determined by second de-
rivative at 270.2 nm. Method B is the first derivative of the ratio spec-
tra spectrophotometric method, ISO can be determined by measuring
the peak amplitude at 227.4 nm using 5 μg mL − 1 of OXD as a divisor,
while TPZ can be determined by measuring the peak amplitude at
249.2 and 261.4 nm using 15 μg mL − 1 of ISO as a divisor. Method C
is the isoabsorptive spectrophotometric method. This method allows
the determination of ISO and TPZ in their binary mixture by measur-
ing total concentration of ISO and TPZ at their isoabsorptive point at
229.8 nm while TPZ concentration alone can be determined at
311.2 nm, then ISO concentration can be determined by subtraction.
On the same basis TPZ can be determined in presence of ISO and
OXD, where OXD concentration alone was determined by measuring
the peak amplitude at 281.6 and 309.4 nm while total concentration
of TPZ and OXD was determined at their isoabsorptive points at
270.2, 310.6 and 331.8 nm then TPZ concentration was determined
by subtraction. Method D is the multivariate calibration techniques
[the classical least squares (CLS), principal component regression
(PCR) and partial least squares (PLS)], using the information con-
tained in the absorption spectra of ISO, TPZ and OXD mixtures.
Derivative and derivative ratio methods were presented by Hassib
et al. [124] for the determination of butamirate citrate, formoterol fu-
marate, montelukast sodium, and sodium cromoglycate. Using the
second DS, butamirate citrate and formoterol fumarate were deter-
mined by measuring the peak amplitude at 260.4 and 261.8 nm, re-
spectively, without any interference of their degradation products.
Butamirate citrate degradation product, 2-phenyl butyric acid, was
determined by the measurement of its second derivative amplitude
at 246.7 nm where butamirate citrate displays zero crossing.
Formoterol fumarate degradation product, desformyl derivative,
could be evaluated through the use of the first derivative at peak am-
plitude of 264.8 nm where interference of formoterol fumarate is
negligible. In the first mode, the zero-crossing technique was applied
at 305 nm for the determination of montelukast sodium in the pres-
ence of its photodegradation product, cis-isomer. The derivative of
ratio spectra of montelukast sodium and its cis-isomer were used to
determine both isomers using the first derivative of the ratio
spectra by measuring the amplitudes of the trough at 305 nm and
the peak at 308 nm, respectively. The later technique was also used
for the determination of a ternary mixture of sodium cromoglycate
and its two degradation products using zero-crossing method. In
the derivative ratio spectra of the ternary mixture, trough depths
were measured at 271.6, 302.8 and 302.2 nm, using the second, the
first, and the second mode to evaluate sodium cromoglycate, degra-
dation product (1) and degradation product (2), respectively.
3.4. Analysis of biological compounds
A first-order DS was applied for the determination of astaxanthin
in Haematococcus pluvialis [125]. Ethyl acetate and ethanol
(1:1, v/v) were found to be the best extraction solvent tested due to
their high efficiency and low toxicity compared with nine other or-
ganic solvents. Astaxanthin coexisting with chlorophyll and
β-carotene was analyzed by first-order DS in order to optimize the
conditions for the determination of astaxanthin. The results show
that when detected at 432 nm, the interfering substances could be
eliminated. On the other hand, the statistical analysis between first-
order DS and HPLC by T-testing did not exceed their critical values, re-
vealing no significant differences between these two methods.
An and Liu establish a DS method for determining the content of
adapalene in liposomes [126]. The first derivative was used to
determine the content of adapalene in liposome with wavelength at
279 nm. The excipients in the liposome did not interfere with the
assay. The results of first DS were not significantly different from
those of HPLC method as analyzed by Paired-Samples T test.
Wang et al. [127] establish a second order DS method for the de-
termination of the content of total iridoid glycoside in Gardenia
jasminoides Ellis from different regions. The second order DS was per-
formed at the wavelength of 263 nm.
An indoor culture experiment was conducted by Zheng et al. to
study the temporal change patterns of chlorophyll content and reflec-
tance spectra of algae from Taihu Lake under different Fe(III) supply
[128]. DS and red edge optical parameter were employed to quantita-
tively extract the algal spectral data, and correlation analysis was
made between the algal spectral data and algal chlorophyll and
Fe(III) contents. Based on these, the quantitative relationship of sup-
plied Fe(III) concentration – algal chlorophyll content – algal spectra
was established. The results showed that supplying appropriate con-
centration Fe(III) was conducive to the algal growth and chlorophyll
synthesis.
The studies developed by Silvestre et al. were an important step in
the process for obtaining rice [129–131] and wheat flour [132,133]
with low phenylalanine content. The authors optimize the enzymatic
protein extraction and hydrolysis, using varied reaction conditions
and the optimization of phenylalanine removal was studied using ac-
tivated carbon as adsorbent and the efficiency of this procedure was
evaluated by the second DS (from 250 to 280 nm). The area of a neg-
ative peak was used to calculate the amount of phenylalanine in the
samples.
In photodynamic therapy by irradiation with light, the porphyrin
used as drugs induced DNA cleavage mainly via singlet oxygen medi-
ated mechanism, and more rarely radical mediated mechanism. Ion
[134] estimated that there are distinct interactions between DNA
and 5,10,15,20-tetra-sulphonated-phenyl-porphyrin by means of
UV–vis derivative spectrophotometry correlated with melting point,
viscosity, and electrophoretic techniques for DNA evaluation.
Magalhaes et al. [135] describe a high-throughput microplate pro-
tocol for assessing the partition coefficients (Kp) of drugs using hexa-
decylphosphocholine micelles as membrane models and DS as the
detection technique. Kp of drugs between the phospholipid bilayer
and the aqueous phase provides useful information in quantitative
structure–activity relationship studies.
The study developed by Brittes et al. [136] gathers a range of spec-
trophotometric and spectrofluorometric techniques to systematically
monitor the effects of resveratrol on the biophysical properties of
membrane model systems consisting of unilamellar liposomes of
phosphatidylcholine with the ultimate goal of relating these effects
with some of the well documented pharmacological properties of
this compound. Kp of resveratrol between liposomes suspensions of
phosphatidylcholine and aqueous solution was determined by DS.
After recording absorption data, the second and third derivatives of
spectra were determined to: eliminate the spectral interferences
due to light scattered by the lipid vesicles; enhance the ability to de-
tect minor spectral features and improve the resolution of bands.
3.5. Food analysis
Anthocyanins (E 163) have been determined in red cabbage,
blackberry, morello cherry, grape and sumac fruit by first order DS
without using any separation or background correction techniques
and reagents [137]. The method is based on the measurement of the
distances between two extreme values, the maximum at 490.5 nm
and the minimum at 550.2 nm (peak-to-peak amplitudes) in the
first order derivative spectra of the extracts.
Determination of vitamin C in fruits and commercial fruit juices
was performed by DS without using any pre-separation or back-
ground correction techniques [138]. The method is based on the
 C. Bosch Ojeda, F. Sanchez Rojas / Microchemical Journal 106 (2013) 1–16
measurement of peak-baseline amplitude in the second derivative
spectra of the extracts at 267.5 nm.
Second DS was used to determine the level and the heat stability of
the three aromatic amino acids (tryptophan, tyrosine and phenylala-
nine) in bovine meat. Gatellier et al. [139] presents a method which
measures the second derivative absorbance values at a wavelength
specifically assigned to each aromatic amino acid with corrections for
the interference from other amino acids at the same wavelength. The
second derivative absorbance of each amino acid was measured by
the vertical distance from baseline to the maximum negative peak of
absorbance. Tryptophan exhibited two peaks, a major one at
288.5 nm and a minor one at 281 nm. Tyrosine exhibited a major
peak at 282.5 nm and a smaller one at 275 nm. Finally, phenylalanine
exhibited a major peak at 263.5 nm and a smaller one at 268 nm.
The application of DS to resolve overlapping spectra and improve
the sensitivity and selectivity of the colorimetric determination of
urea in milk using diacetyl monoxime was presented by Nyanzi et
al. [140]. With first-derivative spectrometry, the λmax of the colored
complex was established to be 525 nm. The absorption band at
λmax = 525 nm in normal absorption spectrometry was resolved
into three clearly distinct spectral bands with minima at 497, 530,
and 566 nm with second-derivative spectrometry. With the second-
derivative technique, the depth of the trough of the strongest signal
at 530 nm was used to determine urea in milk samples.
Synthetic food dyes are usually added to processed foods to give
and restore their desired esthetic quality. This aspect and the toxico-
logical evidence justify quality control and the development of meth-
odologies to quantify these food additives. In this way, Photoacoustic
spectroscopy (PAS) was applied as a method to quantify dyed food
samples, and was compared with first DS [141]. The dyes Brilliant
Blue, Sunset Yellow and Tartrazine, which are common food addi-
tives, were employed for the comparisons. The absorption spectra of
the samples and binary standard mixtures recorded between 400
and 700 nm, first derivative spectra were obtained and the signal at
the zero-crossing points for the binary mixtures was measured, and,
using appropriate working curves, the concentration of each dye in
the different mixtures was determined. Also, PAS allowed the simul-
taneous determination of Brilliant Blue, Sunset Yellow and Tartrazine
as binary mixtures in gelatin and juice powders, with a very good
agreement between the values determined by using first DS. In the
same way, Saad et al. [142] applied DS for the determination of
tartrazine and sunset yellow, in three different kinds of foodstuffs:
juice powders, flavored juices and soft drinks. Also, the mathematical
methodologies such as the additivity principle, derivative spectro-
photometry and multivariate technique (Partial Least Square
Regression — PLSR) were studied in the simultaneous determination
of Tartrazine and Sunset Yellow, extracted from natural wool [143].
These methodologies were evaluated and compared by the authors
according to their prevision capacities. The best PLSR model (spectral
range of 305 to 645 nm with data transformation by first derivative
and two principal components) presented the lower RMSEP (Root
Mean Square Error Prediction) value.
Two methods were described by Ghaedi et al. [144] for simulta-
neous determination of glycyrrhizic acid (GA) and liquiritin (LQ) in
pure and real sample extracted from licorice root without prior sepa-
ration or purification. Method A was based on the first DS, with zero
crossing and graphical (peak to baseline) measurement. The ampli-
tudes at 272.3 and 316.2 nm were selected for the assay of GA and
LQ, respectively. Method B was based on the Vierordt's method in
the binary mixture at first derivative spectra that were calculated by
using the absorbance measured at the same wavelengths.
Methods of derivative spectrophotometry and zero order spectro-
photometry were used to determine energizers in energy drinks. DS
for the determination of caffeine and B vitamins in energy drinks
after solid phase extraction was developed by Pieszko et al. [145].
Caffeine was determined in the mixture with B2 vitamin with zero-
11
crossing technique from the first derivative spectra (λ = 266.8 nm),
and B3 in mixture with B6 vitamin from the second derivative spectra
(λ = 280.1 nm). B12 vitamin has also been determined in a three com-
ponent mixture with vitamins B3 and B6. Taurine in drinks has been
determined from the basic spectra after derivatization with ninhydrin
(λ = 570 nm).
3.6. Environmental analysis
Chen et al. [146] develop a method with ratio spectrum-derivative
spectrophotometry for the determination of chroma in pulping efflu-
ent without adjusting pH value and centrifugation or filtration, thus
operating procedures are simplified, artificial error caused by
human factors is minimized and accuracy of determination is im-
proved. The same research group proposed a high-speed derivative
spectrophotometry–chemometrics method for determination of
chemical oxygen demand (COD) of pulping effluent [147]. In this
method, based on the mathematical relationship between the multi-
wavelength derivative spectral signals and the known COD values of
a set of pulping effluent samples, a calibration model is established
using chemometrics software. With this model, the COD value of a
certain pulping effluent can be easily predicted according to the
multi-wavelength derivative spectral signals.
A DS procedure was developed by Kaur et al. [148] for the deter-
mination of zinc(II) ethylenebisdithiocarbamate, Zineb, after forma-
tion of its blue colored complex with sodium molybdate in acidic
medium. Zineb releases Zn 2+ and its dithiocarbamate unit, the latter
forms a complex with sodium molybdate which is then extracted into
methyl isobutyl ketone and determined by DS. The significant advan-
tage of this method compared to the gas chromatographic methods is
that it can be applied for the direct determination of Zineb in the
presence of other dithiocarbamates like Ziram, Thiram and Ferbam.
The molybdenum complex shows peaks at 670 nm and 956 nm, but
the peak at 956 nm has much higher absorbance; hence all the mea-
surements were made at this wavelength. The first derivative, second
derivative, third derivative and fourth derivative curves were
obtained and the 4th derivative spectra were found to be ideal.
Dyes and pigments represent one of the problematic groups; they
are emitted into wastewaters from various industrial branches, main-
ly from the dye manufacturing and textile finishing and also from
food coloring, cosmetics and paper and carpet industries. Discharge
of dye effluents into the natural streams may be toxic to the aquatic
lives. For this reason, their determination was very important. DS
was one of the most important techniques that can be used to deter-
mine the dye concentration.
The binary mixtures of five textile dyes including yellow, scarlet,
red, blue, and navy blue colors were analyzed by ratio spectra DS
[149]. The absorption spectra of the binary mixtures, prepared in
different ratios, were recorded between 400 and 700 nm. The
obtained spectra were divided by a standard spectrum of each com-
ponent of the binary mixtures, and then the derivative spectra were
calculated. The amounts of dyes were determined by the measure-
ments in the appropriate wavelengths in the range of 400–700 nm.
Ratio spectra DS was introduced as a new approach for achieving
the higher accuracy of determination of dye concentration in bicom-
ponent dye solutions. The developed strategy could be applied in
color industries where fine resolution of bicomponent dye mixtures
is needed.
Gozmen et al. [150] investigate the photocatalytic degradation of
Basic Red 46 (BR46) and Basic Yellow 28 (BY28) dyes in binary mix-
ture. Also, the effects of periodate ion concentration, irradiation time,
initial pH and dye concentration on the photocatalytic degradation
and mineralization of BR46, BY28 by UV/TiO2/IO4− system in single
or binary mixture solutions were examined by the authors. First
order derivative spectrophotometric method, which was a useful
method to solve the overlapped spectra in multi-component systems,
12 C. Bosch Ojeda, F. Sanchez Rojas / Microchemical Journal 106 (2013) 1–16
was used for the simultaneous analysis of BY28 and BR46 dyes in bi-
nary mixtures. BY28 dye could be determined at 380 nm in the pres-
ence of BR46, where the absorbance of BR46 was zero; and BR46 dye
could be determined at 560 nm in the presence of BY28, where the
absorbance of BY28 dye was zero.
Almeida et al. [151] proposed the simultaneous determination of
three dyes: Procion Yellow HE4R, Procion Red HE7B and Remazol
Black 5; these are classified as reactive dyes and are used in the dye-
ing of cotton fibber; by first derivative spectrophotometry in samples
of binary and ternary mixtures. Amplitudes of first-derivative spectra,
from the baseline to the peak, at 395, 604 and 659 nm were propor-
tional to the HE4R, HE7B and RB5 concentrations, respectively.
The main objectives of the study developed by Gao et al. [152]
were the simultaneous analysis of the Yellow 2G (Y2G) and Reactive
Brilliant Red K-2G (RBR) dyes in binary solutions using the first-order
derivative spectrophotometric method and the competitive bio-
sorption of dyes onto inactive aerobic granules. Various mono- and
multi-component isotherm models were applied to evaluate bio-
sorption capacity and competition in the binary solutions. According
to the derivative spectra, the Y2G could be determined at 433 nm,
where the first-order derivative spectrum of RBR was zero; as at
512 nm the first-order derivative spectrum of Y2G was equal to
zero, this wavelength could be selected for RBR.
Principal component analysis (PCA) and DS techniques are used to
improve the accuracy of Beer's law prediction of the concentrations in
three-component dye mixtures [153]. In this work, 180 ternary mix-
tures of dyes were prepared by using Celasol Blue 4GL, Celasol Red
6BL and Celasol Yellow 4RL. The absorbance spectra of samples
were measured from 400 to 700 nm. After computing the mathemat-
ical derivatives of a normal absorbance spectra, the first-order deriv-
ative spectra is confined with 16 wavelengths at 20-nm intervals
from 400 to 700 nm to predict dye concentration by PCA-derivative
technique. In this method, the 16 principal components are extracted
from the first-order derivative absorbance spectra with 16 wave-
lengths. The first three principal components with highest Eigenvalue
are used to predict the dye concentration. The normal- and first-order
derivative absorbance spectra of 100 samples were selected for cali-
bration, and others were used for evaluation performance of predic-
tion. The performance of new method was compared with normal
Beer's law.
The biosorption of Acid Red 274 (AR274) and Acid Red 337
(AR337) dyes from single and binary solutions on Enteromorpha
prolifera was investigated in a single stage batch system by Ozer and
Turabik [154]. The zero order spectrophotometric method was used
for the analysis of the AR274 and AR337 dyes from their single solu-
tions while the first order derivative spectrophotometric method
was applied for the biosorption from binary dyes solution. The
single- and multi-component isotherm models were applied to the
experimental data to determine the biosorbent capacity. AR274 dye
was determined at 591 nm in the presence of AR337, where the ab-
sorbance of AR337 is zero, and AR337 dye was determined at
527 nm in the presence of AR274, where the absorbance of AR274
dye is zero.
3.7. Other analysis
A monitoring method was developed for 2-naphthol to 1,1′-bi-2-
naphthol conversion reaction [155]. The simultaneous monitoring
procedure is based on zero-crossing first DS in basic aqueous media.
Zero-crossing first derivative wavelengths were 359.7 and 345.3 nm,
respectively for 2-naphthol and 1,1′-bi-2-naphthol determinations.
The quantitative results of HPLC and analysis of synthetic mixtures
showed satisfactory compatibility with the results of the proposed
derivative method.
Liu et al. [156] report spontaneous vesicle formation from a cat-
ionic surfactant, dicetyl dimethyl ammonium chloride (DCDAC) and
its mixture with sodium bis-(2-ethylhexyl) sulfosuccinate (AOT) in
different ethanol–water mixed solvents, which have been demon-
strated by the negative-staining transmission electric microscope
(TEM) and the atomic force microscope (AFM) and the entrapment
efficiency of the vesicles to all-trans retinoic acid (ATRA) was mea-
sured by the first order derivative spectrophotometry method at
362 nm.
The biphasic nature of polymeric nanospheres prepared by the
double emulsion method was exploited to co-encapsulate lipophilic
and hydrophilic molecules [157]. ATRA was selected as a lipophilic
drug model whereas calf thymus DNA was chosen as a water-
soluble model. Simultaneous quantification of the loaded ingredients
was achieved by a second derivative spectrophotometric technique.
The experiments achieved showed that the second derivative absor-
bance was useful for the elimination of most interference. Hence,
the spectra of the prepared mixtures were recorded, and the
corresponding second derivative data were computed and plotted.
With each mixture, the amplitude of the valley at 262 nm was mea-
sured for DNA determination in the presence of ATRA, whereas peak
to valley values at 342 and 392 nm, respectively, was summed for
the quantification of ATRA in the presence of DNA.
4. The derivative technique as a tool for green analytical chemistry
Derivative spectroscopy is an analytical technique of great util-
ity for extracting both qualitative and quantitative information
from spectra or chromatograms composed of unresolved bands.
This makes unnecessary the preparation of other samples to obtain
spectra or chromatograms with a higher level of resolution and
thus can achieve significant savings on products and solvents. Al-
though derivative techniques were introduced more 50 years ago
and have demonstrable advantages for the solution of specific
analytical problems, this technique has been accepted only
hesitantly, because of the initial lack of reasonably priced instru-
mentation and original limitation to the first derivative. However,
the introduction of first electronic differentiation by a microcom-
puter interfaced with the spectrophotometer and more recently
the use of a adequate computer for the mathematical treatment
of derivative signal by means of an adequate algorithm makes pos-
sible the plotting of the first, second or higher order derivatives of
a spectrum with respect to wavelength or a chromatogram with
respect to time.
Miniaturization of analytical methods and instrumentation has
resulted in precisely controlled trace level analyses, and their high en-
vironmental compatibility owing to insignificant amount of solvent
and reagent consumption, low waste production, and low operational
cost. Most of the current analytical procedures consist of a
sample preparation step, and quantitation by chromatography and
spectrometry.
Solvent extraction has been most widely used method for sample
preparation. However, the classical mode of solvent extraction per-
formed in a separatory funnel has inconveniences of unfavorable par-
tition equilibria, formation of emulsions, necessity to use large
volume of hazardous and ozone depleting organic solvents and diffi-
culty in waste disposal. Miniaturization of extraction process by
using microliter volumes of the organic solvent has avoided many
of these problems, allowed new ways in which the sample pre-
treatment can be performed.
UV–vis spectrophotometry is a mature analytical technique ap-
plied to many thousands of determinations owing to its simplicity,
flexibility, low cost and convenience. Due to the widespread use of
UV–vis spectrophotometers for routine analysis and as a result of
the great demand to decrease the sample volume needed to perform
a measurement, UV–vis micro-spectrophotometry has been devel-
oped [158].
 C. Bosch Ojeda, F. Sanchez Rojas / Microchemical Journal 106 (2013) 1–16
5. Conclusions
Derivative spectrophotometry is an analytical technique of great
utility for extracting both qualitative and quantitative information
from spectra composed of unresolved bands by calculating and plot-
ting one of the mathematical derivatives of a spectral curve. Therefore
the derivative spectra (first to fourth-order) of the mixtures were
checked to select a suitable spectrum to be used for the simultaneous
determination of the components.
Derivative techniques in spectroscopy often offer a powerful tool for
a resolution enhancement, when signal overlaps or interference exists.
Several specific signals were singled out for the components in the
spectra of different derivative orders but the first-order derivative
spectra seemed to be generally the most suitable for analytical aim.
A derivative spectrum shows better resolution of overlapping
bands than the fundamental spectrum and may permit the accurate
determination of the λmax of the individual bands. Secondly, DS dis-
criminates in favor of substances of narrow spectral bandwidth
against broad bandwidth substances. All the amplitudes in the deriv-
ative spectrum are proportional to the concentration of the analyte
provided that Beer's law is obeyed by the fundamental spectrum.
DS offers a convenient solution to a number of analytical prob-
lems, such as resolution of multicomponent systems, removal of sam-
ple turbidity, matrix background and enhancement of spectral details
and for eliminating the effect of baseline shifts and baseline tilts.
Methods based on processing the spectral data could be applied to
the simultaneous determination of compounds in mixtures without
interference of each other. Chemometric methods are less expensive
by comparison and they do not require sophisticated instrumentation
and any prior separation step, but they need software for calibration
and determination of the component of the mixture.
On the other hand, the combined use of derivative spectrophotom-
etry and chemometric techniques has demonstrated to be a highly con-
venient choice in the determination of multicomponent matrices
presenting serious spectra overlapping, thanks to their common poten-
tial ability to exploit minor spectral features. So, Ultraviolet–visible
spectral data can be transformed in creasing derivative orders so to ob-
tain more useful information. Application of chemometric methods to
derivative UV spectra can magnify the prediction ability of this spectro-
photometric technique.
The DS method has turnaround of a few minutes compared with
other methods, such as HPLC. On the other hand, DS does not require
in almost cases separation steps and the instruments used in the de-
termination of analytes are relatively not expensive and sophisticat-
ed. It does not require an elaborate system and can be easily set up
in manufacturing environment. Also, it is not labor-intensive, does
not require higher skilled personnel, is cheap, is less time consuming,
and, therefore, is very productive.
Derivative techniques were applied for spectrophotometric data
treatment, as a powerful and simple tool, to enhance the accuracy
of both qualitative and quantitative analyses of mixtures. Such an ap-
proach is particularly helpful when the signal is weak or when differ-
ent signals interfere conjointly.
References
[1] F. Sanchez Rojas, C. Bosch Ojeda, J.M. Cano Pavon, Derivative ultraviolet–visible
absorption spectrometry and its analytical applications, Talanta 35 (1988)
753–761.
[2] C. Bosch Ojeda, F. Sanchez Rojas, J.M. Cano Pavon, Recent developments in derivative
ultraviolet/visible absorption spectrophotometry, Talanta 42 (1995) 1195–1214.
[3] C. Bosch Ojeda, F. Sanchez Rojas, Recent developments in derivative
ultraviolet/visible absorption spectrophotometry, Anal. Chim. Acta 518 (2004) 1–24.
[4] F. Sanchez Rojas, C. Bosch Ojeda, Recent development in derivative
ultraviolet/visible absorption spectrophotometry: 2004-2008. A review, Anal.
Chim. Acta 635 (2009) 22–44.
[5] J. Krystek, Determination of analytical wavelength in derivative spectrophotom-
etry, Instrum. Sci. Technol. 37 (2009) 82–88.
13
[6] M. De Luca, F. Oliverio, G. Ioele, G. Ragno, Multivariate calibration techniques ap-
plied to derivative spectroscopy data for the analysis of pharmaceutical mix-
tures, Chemometr. Intell. Lab. Syst. 96 (2009) 14–21.
[7] Y.L. Li, L. Hu, Fractional-order derivative spectroscopy for resolving overlapped
lorenztian peak-signals, ICSP2010 Proceedings, 2010, pp. 211–214.
[8] G. Ugurlu, N. Özaltin, E. Dinç, Spectrophotometric determination of risedronate
sodium in pharmaceutical preparations by derivative and continuous wavelet
transforms, Rev. Anal. Chem. 27 (2008) 215–233.
[9] E. Dinç, G. Pektş, D. Baleanu, Continuous wavelet transform and derivative spec-
trophotometry for the quantitative spectral resolution of a mixture containing
levamizole and triclabendazole in veterinary tablets, Rev. Anal. Chem. 28
(2009) 79–92.
[10] E. Dinç, Y. Kadio lu, F. Demirkaya, D. Baleanu, Continuous wavelet transforms for
simultaneous spectral determination of trimethoprim and sulphamethoxazole
in tablets, J. Iranian Chem. Soc. 8 (2011) 90–99.
[11] K. Belhamel, Selective extraction and determination of Au(III) by first-derivative
spectrophotometry, J. Coord. Chem. 63 (2010) 4290–4298.
[12] G.N. Reddy, K.B. Chandrasekhar, N. Devanna, K.N. Jayaveera, Derivative
spectrophotometric determination of lead(II) using diacetylmonoxime-4-
hydroxybenzoylhydrazone, Asian J. Chem. 20 (2008) 2257–2263.
[13] C.H.K. Devi, D.G. Krishna, N. Devanna, K.B. Chandrasekhar, Direct and deriv-
ative spectrophotometric determination of molybdenum(VI) in presence of
micellar medium in food stuffs, pharmaceutical samples and in alloys using
cinnamaldehyde-4-hydroxy benzoylhydrazone (CHBH), Res. J. Pharm. Biol.
Chem. Sci. 1 (2010) 808–825.
[14] K. Aruna Bai, G.V.S. Vallinath, K.B. Chandrasekhar, N. Devanna, Derivative spec-
trophotometric determination of nickel(II) using 3, 5-dimethoxy-4-hydroxy
benzaldehyde isonicotinoyl hydrazone (DMHBIH), Rasayan J. Chem. 3 (2010)
467–472.
[15] V.K. Kumar, M.R. Rao, K.B. Chandrasekhar, N. Devanna, Derivative spectro-
photometric determination of ruthenium(III) using cinamaldehyde
isonicotinoylhydrazone (CINH), Asian J. Chem. 20 (2008) 2197–2204.
[16] G. Reddy Chandrasekhar, N. Devanna, K.B. Chandrasekhar, Derivative spectro-
photometric determination of ruthenium(III) using diacetyl monoxime iso-
nicotinoyl hydrazone (DMIH), Res. J. Chem. Environ. 15 (2011) 55–58.
[17] K.A. Idriss, H. Sedaira, S.S. Ahmed, Determination of strontium and simultaneous
determination of strontium oxide, magnesium oxide and calcium oxide content
of portland cement by derivative ratio spectrophotometry, Talanta 78 (2009)
81–87.
[18] M. Rameswara Rao, K. Hari, N. Devanna, K.B. Chandrasekhar, Derivative
spectrophotometry determination of Uranium(VI) using 2-hydroxy-3-
methoxybenzaldehydeisonicotinoyl-hydrazone reagent, Asian J. Chem. 20
(2008) 1402–1410.
[19] G.V.S. Vallinath, K.B. Chandra Sekhar, N. Devanna, Direct and derivative
spectrophotometric determination of zinc(II) using 3,5-dimethoxy-4-
hydroxybenzaldehyde isonicotinoyl hydrazone (DMHBIH), Res. J. Pharm. Biol.
Chem. Sci. 1 (2010) 739–749.
[20] A.A. El-Sayed, M.M. Hamed, S.A. El-Reefy, Determination of micro-amounts of
zirconium in mixed aqueous organic medium by normal and first-derivative
spectrophotometry, J. Anal. Chem. 65 (2010) 1113–1117.
[21] M.M. Seleim, M.S. Abu-Bakr, E.Y. Hashem, A.M. El-Zohry, Simultaneous determi-
nation of aluminum(III) and iron(III) by first-derivative spectrophotometry in
alloys, J. Appl. Spectros. 76 (2009) 554–563.
[22] H.R. Pouretedal, P. Sononi, M.H. Keshavarz, A. Semnani, Simultaneous determi-
nation of cobalt and iron using first-derivative spectrophotometric and H-
point standard addition methods in micellar media, Chemistry 18 (2009) 22–35.
[23] K. Vasudeva Reddy, D. Nagarjuna Reddy, K. Hussain Reddy, Derivative spectro-
photometric determination of cobalt(II) and nickel(II) using
2-acetylpyridine-4-methyl-3-thiosemicarbazone (APMT), J. Chem. Pharmaceut.
Res. 3 (2011) 835–839.
[24] K.N. Ghasem, L. Saghatforoush, S. Ershad, Simultaneous determination of copper
and iron in biological samples with l-(2-pvridylazo)-2-naphthol in anionic AOT
micellar solution using derivative spectrophotometry, Asian J. Chem. 21 (2009)
2565–2572.
[25] L.E. Attah, Second derivative spectrophotometry for simultaneous determina-
tion of iron(II) and copper(II) using 2-ketobutyric acid thiosemicarbazone, Indi-
an J. Chem. Tech. 16 (2009) 351–356.
[26] M.T. Alula, A.I. Mohamed, A.A. Bekhit, Simultaneous spectrophotometric deter-
mination of iron (II) and copper (II) in tablets by chemometric methods, Thai.
J. Pharm. Sci. 34 (2010) 93–106.
[27] M.B. Tehrani, E. Souri, Third Derivative Spectrophotometric method for simulta-
neous determination of copper and nickel using 6-(2-naphthyl)-2, 3-dihydro-
1,2,4-triazine-3-thione, E-Journal Chem. 8 (2011) 587–590.
[28] V. Kaur, A.K. Malik, N. Verma, Simultaneous determination of Cu(II) and Pd(II) as
4-phenylpiperazinecarbodithioate complex using H-Point standard addition
method and derivative spectrophotometry, Turk. J. Chem. 34 (2010) 295–305.
[29] A.P. Kumar, P.R. Reddy, V.K. Reddy, Y.I. Lee, Simple and simultaneous method for
determination of palladium(II) and ruthenium(III) using second-order-
derivative spectrophotometry, Anal. Lett. 42 (2009) 84–93.
[30] J. Srinivas, A.B.V. Kiran Kumar, T. Daniel Thangadurai, V. Suryanarayana Rao, Y.J.
Yoo, Y.I. Lee, Non-extractive simultaneous spectrophotometric determination of
trace quantities of palladium(II) and tungsten(VI), Anal. Lett. 44 (2011)
815–823.
[31] Y. Han, Y. Li, W. Si, D. Wei, Z. Yao, X. Zheng, B. Du, Q. Wei, Simultaneous deter-
mination of Cu2+, Zn2+, Cd2+, Hg2+ and Pb2+ by using second-derivative spec-
trophotometry method, Spectrochim. Acta, Part A 79 (2011) 1546–1551.
14 C. Bosch Ojeda, F. Sanchez Rojas / Microchemical Journal 106 (2013) 1–16
[32] L. Quiang, J. Zhou, Determination of nitric oxide using horseradish peroxidise by
UV second-order derivative spectrometry, Anal. Sci. 25 (2009) 1467–1470.
[33] B. Yilmaz, Determination of atenolol in pharmaceutical preparation by zero-,
first-, second- and third-order derivative spectrophotometric methods, Fabad
J. Pharm. Sci. 33 (2008) 119–129.
[34] D. Salman, A. Dogan, N.E. Basci, Spectrophotometric analysis of cabergoline in
pharmaceutical preparations, Lat. Am. J. Pharm. 30 (2011) 304–310.
[35] N.A. Charoo, M. Bashir, E. Abdalla, K.I.H. Ali, Determination of candesartan
cilexetil in tablet dosage forms and dissolution testing samples by first deriva-
tive UV spectrophotometric method, Anal. Lett. 42 (2009) 2232–2243.
[36] N.H. Vadia, N.B. Dobaria, V.B. Patel, conventional and advanced spectrophoto-
metric methods for estimation of cefetamet pivoxil hydrochloride in bulk and
in pharmaceutical formulation, Int. J. ChemTech. Res. 1 (2009) 286–290.
[37] M.D. Game, D.M. Sakarkar, K.B. Gabhane, K.K. Tapar, Validated spectrophoto-
metric methods for the determination of cefuroxime axetil in bulk drug and tab-
lets, Int. J. ChemTech Res. 2 (2010) 1259–1262.
[38] D.G. Dastidar, B. Sa, A comparative study of UV-spectrophotometry and
first-order derivative UV-spectrophotometry methods for the estimation of di-
azepam in presence of tween-20 and propylene glycol, AAPS Pharm Sci Tech
10 (2009) 1396–1400.
[39] B.P. Nagori, P. Khandelwal, S. Sharma, Second derivative spectrophotometric
method for the estimation of drotaverine hydrochloride in tablet formulations,
Indian Drugs 45 (2008) 798–800.
[40] J.C.R. Correa, C. Reichman, H.R.N. Salgado, C.D. Vianna-Soares, Performance char-
acteristics of high performance liquid chromatography, first order derivative UV
spectrophotometry and bioassay for fluconazole determination in capsules,
Quim. Nova 35 (2011) 530–534.
[41] D. Madhuri, K.B. Chandrasekhar, N. Devanna, G. Somasekhar, Direct and deriva-
tive spectrophotometric estimation of gemifloxacin by chelation with
palladium(II) ion, Rasayan J. Chem. 3 (2010) 159–165.
[42] D. Madhuri, K.B. Chandrasekhar, N. Devanna, G. Somasekhar, Direct and deriva-
tive spectrophotometric estimation of gemifloxacinmesylate by chelation with
Cr(III) ion, Rasayan J. Chem. 3 (2010) 9–15.
[43] J. Krzek, H. Woltyńska, U. Hubicka, Determination of gentamicin sulphate in in-
jection solutions by derivative spectrophotometry, Anal. Lett. 42 (2009)
473–482.
[44] S.K. Acharjya, P. Mallick, P. Panda, K.R. Kumar, M.M. Annapurna, Spectrophoto-
metric methods for the determination of letrozole in bulk and pharmaceutical
dosage forms, J. Adv. Pharm. Tech. Res. 1 (2010) 348–353.
[45] R. Bonfilio, L.B. Favoretto, G.R. Pereira, R.D.C.P. Azevedo, M.B. De Araújo, Com-
parative study of analytical methods by direct and first derivative UV spectro-
photometry for evaluation of losartan potassium in capsules, Brazilian J.
Pharm. Sci. 46 (2010) 147–155.
[46] S.M. Malipatil, M. Deepthi, S.K. Patil, K. Jahan, Second and third order derivative
spectrophotometric estimation of nebivolol hydrochloride in bulk and pharma-
ceutical dosage forms, Int. J. Pharm. Pharm. Sci. 3 (2011) 13–15.
[47] B. Szaniszlo, C. Iuga, M. Bojita, Indirect determination of neomycin by derivative
spectrophotometry, Farmacie 84 (2011) 398–401.
[48] M. Koba, K. Koba, T. Baczek, Determination of oxazepam in pharmaceutical for-
mulation by HPTLC UV-densitometric and UV-derivative spectrophotometry
Methods, Anal. Lett. 42 (2009) 1831–1843.
[49] S.T. Ulu, F.T. Elmali, UV-second derivative spectrophotometric and colorimetric
methods for the determination, validation and thermogravimetric analysis of
new oral antidiabetic pioglitazone in pure and pharmaceutical preparations,
Anal. Lett. 42 (2009) 2254–2270.
[50] C.N. Raju, G.D. Rao, R. Sikharam, UV and two derivative spectrometric methods
for determination of racecadotril in tablet formulation, Biosci. Biotechnol. Res.
Asia 5 (2008) 747–752.
[51] A. Sokół, J. Karpińska, R. Talecka, B. Starczewska, Quantification of ranitidine hy-
drochloride in the presence of its decomposition product by spectrophotometric
methods. Application for kinetic study, Acta Pol. Pharm. Drug Res. 68 (2011)
169–177.
[52] C.L. Dias, A.M. Bergold, P.E. Fröehlich, UV-Derivative spectrophotometric deter-
mination of ritonavir capsules and comparison with LC method, Anal. Lett. 42
(2009) 1900–1910.
[53] A.S. Atul, H.B. Charushila, J.S. Sanjay, Determination of tenofovir in pharmaceutical for-
mulation by zero order and first order derivative UV-spectrophotometry methods,
Res. J. Chem. Environ. 12 (2008) 49–50.
[54] A.S. Atul, H.B. Charushila, J.S. Sanjay, Application of UV-spectrophotometric
methods for estimation of tenofovir disoproxil fumarate in tablets, Pak. J.
Pharm. Sci. 22 (2009) 27–29.
[55] A. Kucuk, Y. Kadioglu, Determination of tramadol hydrochloride by using UV
and derivative spectrophotometric methods in human plasma, Asian J. Chem.
23 (2011) 663–667.
[56] L. Du, M. Li, Y. Jin, Determination of triclosan in antiperspirant gels by first-order
derivative spectrophotometry, Pharmazie 66 (2011) 740–743.
[57] A. Nikam, S. Pawar, S. Gandhi, Estimation of paracetamol and aceclofenac in tab-
let formulation by ratio spectra derivative spectroscopy, Indian J. Pharmaceut.
Sci. 70 (2008) 635–637.
[58] S.J. Gondane, M.M. Deshpande, M.P. Mahajan, S.D. Sawant, Spectrophotometric
method development and validation for estimation of tizanidine and ace-
clofenac in bulk drug & tablet formulation, Int. J. ChemTech Res. 3 (2011)
620–624.
[59] H. Khajehsharifi, Z. Eskandari, A. Asadipour, Application of some chemometric
methods in conventional and derivative spectrophotometric analysis of acet-
aminophen and ascorbic acid, Drug Test. Anal. 2 (2010) 162–167.
[60] M.I. Toral, J. Rivas, M. Saldías, C. Soto, S. Orellana, Simultaneous determination of
acetaminophen and tramadol by second derivative spectrophotometry, J. Chil-
ean Chem. Soc. 53 (2008) 1543–1548.
[61] C. Soto, D. Contreras, S. Orellana, J. Yañez, M.I. Toral, Simultaneous determina-
tion of albendazole and praziquantel by second derivative spectrophotometry
and multivariated calibration methods in veterinary pharmaceutical formula-
tion, Anal. Sci. 26 (2010) 891–896.
[62] M.A. El-Sayed, Determination of binary mixture of raubasine and almitrine dis-
mesylate by derivative spectrophotometry, Saudi Pharmaceut. J. 17 (2009)
62–69.
[63] S. Patel, N.J. Patel, Spectrophotometric and chromatographic simultaneous esti-
mation of amitriptyline hydrochloride and chlordiazepoxide in tablet dosage
forms, Indian J. Pharmaceut. Sci. 71 (2009) 472–476.
[64] V.T. Huong, V.D. Hoang, Simultaneous determination of amoxicillin and
clavulanate in combined tablets by non-derivative and derivative UV spectro-
photometric techniques, Int. J. Pharm. Tech. Res. 1 (2009) 1173–1181.
[65] D.T. Giang, V.D. Hoang, Comparative study of RP-HPLC and UV spectrophoto-
metric techniques for the simultaneous determination of amoxicillin and cloxa-
cillin in capsules, J. Young Pharm. 2 (2010) 190–195.
[66] J. Karpińska, A. Sokół, M. Rozko, Applicability of derivative spectrophotometry,
bivariate calibration algorithm, and the Vierordt method for simultaneous de-
termination of ranitidine and amoxicillin in their binary mixtures, Anal. Lett.
42 (2009) 1203–1218.
[67] R. Hajian, N. Shams, I. Kaedi, Application of ratio derivative spectrophotometry
for simultaneous determination of naphazoline and antazoline in eye drops,
E-Journal Chem. 7 (2010) 1530–1538.
[68] V. Patel, R. Baldha, D. Patel, Simultaneous determination of atorvastatin calcium
and ezetimib by ratio spectra derivative spectrophotometry and reverse
phase-high performance liquid chromatography, Asian J. Chem. 22 (2010)
2511–2517.
[69] B.O. Silva, First derivative spectrophotometric and high performance liquid
chromatographic simultaneous determination of benzoic and salicylic acids in
pharmaceutical preparations, Niger. Q. J. Hosp. Med. 18 (2008) 92–95.
[70] B. Ganesan, P. Perumal, V. Manickam, S.R. Srikakolapu, S.D. Gotteti, L.S.
Thirumurthy, Simultaneous determination of strychnine and brucine in herbal
formulation by UV derivative spectrophotometry, Int. J. Pharm. Tech. Res. 2
(2010) 1528–1532.
[71] H. Tavallali, M. Salami, Simultaneous determination of caffeine and paracetamol
by zero-crossing second derivative spectrophotometry in pharmaceutical prep-
arations, Asian J. Chem. 21 (2009) 1949–1956.
[72] M. Sultan, Simultaneous determination of carvedilol and hydrochlorothiazide in
tablets by derivative spectrophotometric and HPLC methods, Asian J. Chem. 20
(2008) 2283–2292.
[73] R.P. Patel, A.F. Mehta, Estimation of cetrizine hydrochloride & phenylpropanol-
amine hydrochloride in combined dosage form by 2nd order derivative spectro-
photometry and dual wavelength spectroscopic method, IJPI's J. Anal. Chem. 1
(2010) 1–9.
[74] S. Patel, N.J. Patel, S.A. Patel, Simultaneous spectrophotometric estimation of imipra-
mine hydrochloride and chlordiazepoxide in tablets, Indian J. Pharmaceut. Sci. 71
(2009) 468–472.
[75] O.A. Donmez, A. Bozdogan, G. Kunt, Y. Div, Spectrophotometric multicomponent
analysis of a mixture of chlorhexidine hydrochloride and lidocaine hydrochlo-
ride in pharmaceutical formulation using derivative spectrophotometry and
partial least-squares multivariate calibration, J. Anal. Chem. 65 (2010) 30–35.
[76] C. Soto, D. Contreras, M.I. Toral, L. Basaez, J. Freerc, Simultaneous determination
of dibucaine and chlorphenamine maleate using different mathematical spec-
trophotometric approaches, J. Chilean Chem. Soc. 54 (2009) 113–118.
[77] S.B. Wankhede, V.S. Gadewar, V. Thombre, S.S. Chitlange, Derivative spectropho-
tometric method for the simultaneous determination of ciprofloxacin and
ornidazole in tablet dosage form, Indian Drugs 45 (2008) 426–429.
[78] M.R. Sohrabi, P. Abdolmaleki, E.A. Esmaeili, Simultaneous spectrophotometric
determination of cyproterone acetate and ethinyl estradiol in tablets using con-
tinuous wavelet and derivative transform, Spectrochim. Acta. Part A 77 (2010)
107–111.
[79] S. Caglar, S.E. Toker, Simultaneous determination of desloratadine and pseudo-
ephedrine sulphate in tablets by high performance liquid chromatography and
derivative spectrophotometry, Rev. Anal. Chem. 30 (2011) 145–151.
[80] E. Karacan, M.G. Çaĝlayan, I.M. Palabiyik, F. Onur, Liquid chromatographic and
spectrophotometric determination of diflucortolone valerate and isoconazole
nitrate in creams, J. AOAC Int. 94 (2011) 128–135.
[81] R.G. Baldha, B. Patel Vandana, M. Bapna, Simultaneous spectrophotometric esti-
mation of rabeprazole sodium and domperidone in combined dosage forms, Int.
J. Pharm. Tech. Res. 2 (2010) 1563–1568.
[82] A.H. Patel, J.K. Patel, K.N. Patel, Development and validation of derivative spec-
trophotometric method for simultaneous estimation of domperidone and
rabeprazole sodium in bulk and dosage forms, Int. J. Pharm. Sci. 2 (2010)
464–469.
[83] H.M. Chawla, S. Mrig, Simultaneous quantitative estimation of oxybenzone and
2-ethylhexyl-4-methoxycinnamate in sunscreen formulations by second order
derivative spectrophotometry, J. Anal. Chem. 64 (2009) 585–592.
[84] A.K. Gajjar, V.D. Shah, Simultaneous estimation of rosuvastatin and ezetimibe by
ratio spectra derivative spectrophotometry method in their fixed dosage forms,
Int. J. Pharm. Tech. Res. 2 (2010) 404–410.
[85] K. Anandakumar, K. Kannan, T. Vetrichelvan, Simultaneous determination of
simvastatin and ezetimibe in tablet formulation by derivative spectrophotome-
try, Indian J. Pharm. Educ. Res. 42 (2008) 122–126.
 C. Bosch Ojeda, F. Sanchez Rojas / Microchemical Journal 106 (2013) 1–16
[86] E. Souri, M. Amanlou, Development and validation of a derivative spectrophoto-
metric method for simultaneous determination of simvastatin and ezetimibe,
E-Journal Chem. 7 (2010) S197–S202.
[87] F.F. Belal, M.K.S. El-Din, F.A. Aly, M.M. Hefnawy, M.I. El-Awady, Spectrophoto-
metric analysis of a mixture of glyburide and metformin hcl in pharmaceutical
preparations, Der Pharma Chemica 3 (2011) 53–64.
[88] R. Hajian, N. Shams, Z. Davarpanah, Combination of first derivative spectropho-
tometry and H-point standard addition method for simultaneous determination
of guaifenesin and theophylline in cough syrup, E-Journal Chem. 8 (2011)
966–976.
[89] M.I. Toral, S. Orellana, M. Saldías, C. Soto, Strategies used to develop analytical
methods for simultaneous determination of organic compounds by derivative
spectrophotometry, Quim. Nova 32 (2009) 257–262.
[90] D.A. Shah, K.K. Bhatt, R.S. Mehta, S.L. Baldania, Determination of nebivolol hy-
drochloride and hydrochlorothiazide in tablets by first-order derivative spectro-
photometry and liquid chromatography, J. AOAC Int. 91 (2008) 1075–1082.
[91] A.R. Rote, P.D. Bari, Ratio spectra derivative and zero-crossing difference spec-
trophotometric determination of olmesartan medoxomil and hydrochlorothia-
zide in combined pharmaceutical dosage form, AAPS Pharm. Sci. Tech. 10
(2009) 1200–1205.
[92] K. Mohammadpour, M.R. Sohrabi, A. Jourabchi, Continuous wavelet and deriva-
tive transform applied to the overlapping spectra for the quantitative spectro-
photometric multi-resolution of triamterene and hydrochlorothiazide in
triamterene-H tablets, Talanta 81 (2010) 1821–1825.
[93] P. Rai, P. Patil, S.J. Rajput, Simultaneous determination of phyllanthin and hypo-
phyllanthin in herbal formulation by derivative spectrophotometry and liquid
chromatography, Pharmacogn. Mag. 4 (2009) 151–158.
[94] V.J. Guzsvány, Z.J. Papp, S.D. Lazić, F.F. Gaál, L.J. Bjelica, B.F. Abramović, A rapid
spectrophotometric determination of imidacloprid in selected commercial for-
mulations in the presence of 6-chloronicotinic acid, J. Serb. Chem. Soc. 74
(2009) 1455–1465.
[95] D. Bageshwar, A. Pawar, V. Khanvilkar, V. Kadam, Simultaneous determination
of pantoprazole sodium and itopride hydrochloride in pharmaceutical dosage
form by first order derivative UV spectrophotometry, Asian J. Pharm. Clin. Res.
3 (2010) 221–223.
[96] A.R. Rote, V.S. Niphade, Determination of montelukast sodium and levocetirizine
dihydrochloride in combined tablet dosage form by HPTLC and first-derivative
spectrophotometry, J. Liq. Chrom. Relat. Tech. 34 (2011) 155–167.
[97] D. Nagavalli, R. Rajeevkumar, P. Kumar, T. Devi, Derivative spectrophotometric
estimation of levofloxacin hemihydrate and ornidazole, Int. J. Chem. Tech. Res.
2 (2010) 2145–2149.
[98] I. Draghici, A. Nedelcu, C.M. Monciu, C. Aramc, Derivative spectrometry in the
assay of simvastatin and lovastatin, Farmacia 56 (2008) 5–14.
[99] A. Pomykalski, H. Hopkała, Comparison of classic and derivative UV spectropho-
tometric methods for quantification of meloxicam and mefenamic acid in phar-
maceutical preparations, Acta Pol. Pharm. Drug Res. 68 (2011) 317–323.
[100] A. Önal, Spectrophotometric and HPLC determinations of anti-diabetic drugs,
rosiglitazone maleate and metformin hydrochloride, in pure form and in phar-
maceutical preparations, Eur. J. Med. Chem. 44 (2009) 4998–5005.
[101] F.I. Khattab, N.K. Ramadan, M.A. Hegazy, N.S. Ghoniem, Simultaneous determi-
nation of metronidazole and spiramycin in bulk powder and in tablets using dif-
ferent spectrophotometric techniques, Drug Test. Anal. 2 (2010) 37–44.
[102] S.V. Gandhi, J.V. Shah, A.D. Nikam, V. Vaidyanathan, Estimation of ofloxacin and
tinidazole in tablet formulation by ratio spectra derivative spectroscopy, Indian
J. Pharm. Educ. Res. 42 (2008) 70–73.
[103] M.I. Toral, S.L. Orellana, C.A. Soto, P. Richter, Extraction and determination of
oxytetracycline hydrochloride and oxolinic acid in fish feed by derivative spec-
trophotometry of first order, Food Anal. Meth. 4 (2011) 497–504.
[104] S. Sardana, R.C. Mashru, Simultaneous determination of phenylephrine hydro-
chloride and tropicamide in ophthalmic dosage form with three rapid derivative
spectrophotometric methods, J. Chilean Chem. Soc. 55 (2010) 515–518.
[105] R. Hajian, R. Haghighi, N. Shams, Combination of ratio derivative spectropho-
tometry with simultaneous standard additions method for determination of sul-
famethoxazole and trimethoprim, Asian J. Chem. 22 (2010) 6569–6579.
[106] M.H. Abdel-Hay, A.A. Gazy, E.M. Hassan, T.S. Belal, Derivative and derivative
ratio spectrophotometric analysis of antihypertensive ternary mixture of
amiloride hydrochloride, hydrochlorothiazide and timolol maleate, J. Chin.
Chem. Soc. 55 (2008) 971–978.
[107] A. Pathak, S. Rajput, Simultaneous derivative spectrophotometric analysis of
doxylamine succinate, pyridoxine hydrochloride and folic acid in combined dos-
age forms, Indian J. Pharmaceut. Sci. 70 (2008) 513–517.
[108] A. Chandratrey, R. Sharma, Simultaneous spectrophotometric estimation and
validation of three component tablet formulation containing paracetamol,
nimesulide and tizanidine, Indian J. Chem. Technol. 17 (2010) 229–232.
[109] M. Stolarczyk, A. Apola, J.A.N. Krzek, A. Sajdak, Validation of derivative spectro-
photometry method for determination of active ingredients from neuroleptics
in pharmaceutical preparations, Acta Pol. Pharm. Drug Res. 66 (2009) 351–356.
[110] G. Ioele, F. Oliverio, I. Andreu, M. De Luca, M.A. Miranda, G. Ragno, Different
photodegradation behavior of barnidipine under natural and forced irradiation,
J. Photochem. Photobiol A: Chem. 215 (2010) 205–213.
[111] J. Cielecka-Piontek, A. Lunzer, A. Jelińska, Stability-indicating derivative spectro-
photometry method for the determination of biapenem in the presence of its
degradation products, Cent. Eur. J. Chem. 9 (2011) 35–40.
[112] N.A. Al-Arfaj, W.A. Al-Onazi, A.M. El-Brashy, Spectrophotometric determination
of candesartan cilexetil in presence of its alkaline induced degradation product,
Asian J. Chem. 23 (2011) 1696–1700.
15
[113] H.E. Zaazaa, S.S. Abbas, M. Abdelkawy, M.M. Abdelrahman, Spectrophotometric
and spectrodensitometric determination of clopidogrel bisulfate with kinetic
study of its alkaline degradation, Talanta 78 (2009) 874–884.
[114] M. Nebsen, M.K. Abd El-Rahman, M.Y. Salem, A.M. El-Kosasy, M.G. El-Bardicy,
Stability-indicating spectrophotometric and spectrodensitometric methods for
the determination of diacerein in the presence of its degradation product,
Drug Test. Anal. 3 (2011) 221–227.
[115] J. Cielecka-Piontek, A. Jelińska, The UV-derivative spectrophotometry for the
determination of doripenem in the presence of its degradation products,
Spectrochim. Acta, Part A 77 (2010) 554–557.
[116] N.Y. Hassan, E.M. Abdel-Moety, N.A. Elragehy, M.R. Rezk, Selective determina-
tion of ertapenem in the presence of its degradation product, Spectrochim.
Acta Part A 72 (2009) 915–921.
[117] S.M. El-Moghazy, M.A. El-Azem Mohamed, M.F. Mohamed, N.F. Youssef, Devel-
opment and validation of HPLC, TLC and derivative spectrophotometric methods
for the analysis of ezetimibe in the presence of alkaline induced degradation
products, J. Chin. Chem. Soc. 56 (2009) 360–367.
[118] H.M. Lotfy, M.M.A. El-Moneim Abosen, M.G. EL-Bardicy, Stability-indicating
methods for the determination of famciclovir in the presence of its
alkaline-induced degradation product, Drug Test. Anal. 2 (2010) 188–199.
[119] B. Markovic, S. Vladimirov, O. Cudina, V. Savic, K. Karljikovic-Rajic, An applica-
tion of second-order UV-derivative spectrophotometry for study of solvolysis
of a novel fluocinolone acetonide ester, Spectrochim. Acta Part A 75 (2010)
930–935.
[120] A.O. Mohamed, M.M. Fouad, M.M. Hasan, S.A. Abdel Razeq, Z.A. Elsherif,
Stability-indicating methods for the determination of racecadotril in the pres-
ence of its degradation products, Biosci. Trends 3 (2009) 247–252.
[121] L.S. Abdel-Fattah, Z.A. El-Sherif, K.M. Kilani, D.A. El-Haddad, HPLC, TLC, and
first-derivative spectrophotometry stability-indicating methods for the deter-
mination of tropisetron in the presence of its acid degradates, J. AOAC Int. 93
(2010) 1180–1191.
[122] M.A. El-Sayed, Stability-indicating methods for the determination of a mixture
of almitrine and raubasine by derivative spectrophotometry, Drug Test. Anal. 1
(2009) 279–285.
[123] S.S. Abbas, H.E. Zaazaa, M. Abdelkawy, M.M. Abdelrahman, Spectrophotometric
determination of isopropamide iodide and trifluoperazine hydrochloride in
presence of trifluoperazine oxidative degradate, Drug Test. Anal. 2 (2010)
168–181.
[124] S.T. Hassib, A.A. El-Zaher, M.A. Fouad, Validated stability-indicating derivative
and derivative ratio methods for the determination of some drugs used to alle-
viate respiratory tract disorders and their degradation products, Drug Test. Anal.
3 (2011) 306–318.
[125] L.X. Juan, W.Y. Hua, Z.L. Zhao, S. Xiao, Z.A. Mei, A. Xin, Determination of
astaxanthin in haematococcus pluvialis by first-order derivative spectropho-
tometry, J. AOAC Int. 94 (2011) 1752–1757.
[126] Y.C. An, L.P. Liu, Determination of adapalene content in liposomes by first deriv-
ative uv spectrophotometry, Chinese J. New Drugs 19 (2010) 534–536.
[127] L. Wang, X. Wang, S. Wang, T. Zhou, G. Fan, Determination of the content of total
iridoid glycoside in Gardenia jasminoides Ellis by second order derivative spec-
trophotometry, Pharmaceut. Care Res. 10 (2010) 205–207.
[128] T.H. Zheng, Y. Shi, G.Y. Chi, X. Chen, Effects of Fe(III) on the growth and spectral
characteristics of algae, Chinese J. Ecol. 29 (2010) 2471–2476.
[129] M.P.C. Silvestre, C.R. Vieira, M.R. Silva, R.L. Carreira, V.D.M. Silva, H.A. Morais,
Protein extraction and preparation of protein hydrolysates from rice with low
phenylalanine content, Asian J. Sci. Res. 2 (2009) 146–154.
[130] M.P.C. Silvestre, C.R. Vieira, M.R. Silva, M.C. Silva, C.O. Lopes Jr., V.D.M. Silva, Use
of an enzymatic process for extracting and hydrolyzing rice proteins aiming at
phenylalanine removal, Int. J. Food Eng. 5 (2009) 1–11.
[131] R.L. Carreira, C.S. Ramos, L.A. Mundim, M.R. Silva, V.D.M. Silva, M.P.C. Silvestre,
Effect of enzyme type, mode of enzyme action and temperature on the
obtention of low phenylalanine hydrolysates from wheat flour, Am. J. Food
Tech. 4 (2009) 71–78.
[132] R.L. Carreira, V.D.M. Silva, J.N. Januário, M.J.B. De Aguiar, A.L.P. Starling, M.P.C.
Silvestre, Action of enzymatic factors in obtaining protein hydrolysates from
wheat flour with low phenylalanine, Brazilian J. Pharm. Sci. 45 (2009) 93–98.
[133] R.L. Carreira, C.S. Ramos, A.B. de Vasconcelos, M.M. Santoro, M.P.C. Silvestre, Ef-
fect of hydrolytic parameters in obtaining of protein hydrolysates of wheat flour
with low phenylalanine content, Cienc. Technol. Aliment. 30 (2010) 152–157.
[134] R.M. Ion, Derivative UV-Vis spectrophotometry for porphyrins interactions in
photodynamic therapy, Anal. Lett. 43 (2010) 1277–1286.
[135] L.M. Magalhães, C. Nunes, M. Lúcio, M.A. Segundo, S. Reis, J.L.F.C. Lima,
High-throughput microplate assay for the determination of drug partition coef-
ficients, Nat. Protoc. 5 (2010) 1823–1830.
[136] J. Brittes, M. Lúcio, C. Nunes, J.L.F.C. Lima, S. Reis, Effects of resveratrol on mem-
brane biophysical properties: relevance for its pharmacological effects, Chem.
Phys. Lipids 163 (2010) 747–754.
[137] D. Şakar, G.K. Karaoglan, G. Gümrükçü, M.Ü. Özgür, Determination of anthocya-
nins in some vegetables and fruits by derivative spectrophotometric method,
Rev. Anal. Chem. 27 (2008) 235–249.
[138] N.Z. Blagojeviæ, V.L. Vukašinoviæ-Pešiæ, Determination of vitamin C in fruits
and commercial fruit juices by derivative spectrophotometry, Res. J. Chem.
Environ. 12 (2008) 18–22.
[139] P. Gatellier, A. Kondjoyan, S. Portanguen, E. Grève, K. Yoon, V. Santé-Lhoutellier,
Determination of aromatic amino acid content in cooked meat by derivative
spectrophotometry: implications for nutritional quality of meat, Food Chem.
114 (2009) 1074–1078.
16 C. Bosch Ojeda, F. Sanchez Rojas / Microchemical Journal 106 (2013) 1–16
[140] S.A. Nyanzi, M. Isiko, F. Kateregga, W. Schwack, Second-derivative spectrometric
determination of urea in milk using the diacetyl monoxime reagent, J. AOAC Int.
93 (2010) 485–491.
[141] T.M. Coelho, E.C. Vidotti, M.C. Rollemberg, A.N. Medina, M.L. Baesso, N. Cella, A.C.
Bento, Photoacoustic spectroscopy as a tool for determination of food dyes:
comparison with first derivative spectrophotometry, Talanta 81 (2010)
202–207.
[142] A. Saad, S. Nazira, A. Rasha, Determination of tartrazine and sunset yellow in
foodstuffs by derivative spectrophotometric method, Asian J. Chem. 23 (2011)
1825–1828.
[143] M.E. dos Santos, I.M. Demiate, N. Nagata, Simultaneous determination of
tartrazine and sunset yellow in food by spectrophotometry UV–VIS and multi-
variate calibration methodology, Cienc. Technol. Aliment. 30 (2010) 903–909.
[144] A. Ghaedi, S.S. Madaeni, M.R. Sohrabi, M. Khosravi, Simultaneous determination
of glycyrrhizic acid and liquiritin in licorice root using first derivative
spectrophotometric and Vierordt's method, Fresen. Environ. Bull. 20 (2011)
1406–1413.
[145] C. Pieszko, I. Baranowska, A. Flores, Determination of energizers in energy
drinks, J. Anal. Chem. 65 (2010) 1228–1234.
[146] H. Chen, Y. Chen, H. Zhan, S. Fu, Determination of chroma in pulping effluent by
ratio spectrum-derivative spectrophotometry, Environ. Prog. Sustain. Energy 29
(2010) 342–348.
[147] H.L. Chen, Y.C. Chen, H.Y. Zhan, S.Y. Fu, Determination of pulping effluent cod
using derivative spectrophotometry–chemometrics method, Huanan Ligong
Daxue Xuebao 37 (2009) 150–154.
[148] M. Kaur, V. Kaur, A.K. Malik, N. Verma, B. Singha, A.L.J. Rao, Development of a de-
rivative spectrophotometric method for the determination of fungicide zinc
ethylenebisdithiocarbamate using sodium molybdate, J. Brazil. Chem. Soc. 20
(2009) 993–998.
[149] A.S. Nateri, E. Ekrami, Quantitative analysis of bicomponent dye solutions by de-
rivative spectrophotometry, Pigm. Resin Technol. 38 (2009) 43–48.
[150] B. Gözmen, M. Turabik, A. Hesenov, Photocatalytic degradation of basic red 46
and basic yellow 28 in single and binary mixture by UV/TiO2/periodate system,
J. Hazard. Mater. 164 (2009) 1487–1495.
[151] V.C. Almeida, A.M.M. Vargas, J.C. Garcia, E. Lenzi, C.C. Oliveira, J. Nozaki, Simulta-
neous determination of the textile dyes in industrial effluents by first-order de-
rivative spectrophotometry, Anal. Sci. 25 (2009) 487–492.
[152] J.F. Gao, Q. Zhang, K. Su, J.H. Wang, Competitive biosorption of yellow 2G and re-
active brilliant red K-2G onto inactive aerobic granules: simultaneous determi-
nation of two dyes by first-order derivative spectrophotometry and isotherm
studies, Bioresour. Technol. 101 (2010) 5793–5801.
[153] A. Shams-Nateri, Prediction of dye concentrations in a three-component dye
mixture solution by a PCA-derivative spectrophotometry technique, Color. Res.
Appl. 35 (2010) 29–33.
[154] A. Özer, M. Turabik, Competitive biosorption of acid dyes from binary solutions
onto enteromorpha prolifera: application of the first order derivative spectro-
photometric analysis method, Sep. Sci. Technol. 45 (2010) 380–393.
[155] K. Shayesteh, J. Moghaddas, M. Haghighi, H. Eskandari, Development of a mon-
itoring method for oxidative coupling reaction of 2-naphthol in solid state,
Asian J. Chem. 22 (2010) 2106–2116.
[156] F. Liu, Z.W. Wang, M.Y. Gu, Z.N. Wang, Entrapment efficiency of all-trans retinoic
acid in surfactant vesicles, J. Dispersion Sci. Technol. 30 (2009) 1442–1448.
[157] T. Hammady, A. El-Gindy, E. Lejmi, R.S. Dhanikula, P. Moreau, P. Hildgen, Charac-
teristics and properties of nanospheres co-loaded with lipophilic and hydrophil-
ic drug models, Int. J. Pharm. 369 (2009) 185–195.
[158] J.M. Cano Pavón, A. García de Torres, C. Bosch Ojeda, F. Sánchez Rojas, E.I. Vereda
Alonso, Derivative techniques in molecular absorption, fluorimetry and liquid chro-
matography as tool for green analytical chemistry, Handbook of Green Analytical
Chemistry, first edition, John Wiley & Sons, 2012, pp. 245−259–245−259.