Volumetric analysis of some

antineoplastic drugs

Prepared by

Joyce Yousry Sobhy

Supervised by

Dr/ Ebrthal Samir

Quantitative chemical analysis

Quantitative chemical analysis, branch of chemistry that deals

with the determination of the amount or percentage of one or
more constituents of a sample. A variety of methods is
employed for quantitative analyses, which for convenience
may be broadly classified as chemical or physical, depending
upon which properties are utilized. Chemical methods depend
upon such reactions as precipitation, neutralization, oxidation,
or, in general, the formation of a new compound. The major
types of strictly chemical methods are known as gravimetric
analysis and volumetric, or titrimetric, analysis (see volumetric
analysis). Physical methods involve the measurement of some
physical property such as density, refractive index, absorption
or polarization of light, electromotive force, magnetic
susceptibility, and numerous others. An analysis will often
require a combination of methods: qualitative for separating
desired constituents from a sample and quantitative for
measuring the amounts present.

Volumetric Analysis

Volumetric analysis, any method of quantitative chemical

analysis in which the amount of a substance is determined by
measuring the volume that it occupies or, in broader usage,
the volume of a second substance that combines with the first

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in known proportions, more correctly called titrimetric analysis
(see titration).

The first method is exemplified in a procedure devised by a

French chemist, Jean-Baptiste-André Dumas, for determining
the proportion of nitrogen combined with other elements in
organic compounds. A weighed sample of the compound is
burned in a furnace under conditions that ensure the
conversion of all the nitrogen to elemental nitrogen gas, N2.
The nitrogen is carried from the furnace in a stream of carbon
dioxide that is passed into a strong alkali solution, which
absorbs the carbon dioxide and allows the nitrogen to
accumulate in a graduated tube. The mass of the nitrogen can
be calculated from the volume it occupies under known
conditions of temperature and pressure, and therefore the
proportion of nitrogen in the sample can be determined.

A volumetric method is also applied in the analysis of nitrates,

which can be converted into nitric oxide, NO, a gas. Production
or consumption of carbon dioxide during biological processes
often is measured volumetrically. The composition of fuel
gases and combustion products can be determined by
measuring the changes in volume that occur when the sample
is treated successively with reagents that specifically absorb
such components as carbon dioxide, carbon monoxide,
oxygen, and others.

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What Is an Antineoplastic Drug?

Cancer is an extremely common disease, which impacts an

untold number of people (and animals) each year. The
abnormal cell division caused by cancers can impact virtually
any body system, unlike other diseases that may only impact a
single organ. In many cases, multiple systems are impacted at
the same time.

So how do we treat a disease that can take so many different

forms? We use a special group of medicines called
antineoplastic drugs that can range in form from antibiotics to
chemotherapy agents.

How Do Antineoplastic Drugs Work?

Antineoplastic drugs are medicines that are used to treat some

forms of cancer. Most drugs on the market are designed to kill
only a specific type of bacteria or virus, but antineoplastic
drugs have to target a wide range of cells over sometimes
multiple body systems. As a result, anti-cancer drugs often
harm healthy cells in an attempt to kill the cancer cells.

Antineoplastic drugs are different from the over-the-counter

drugs you might take for a cold or allergies. Those drugs target
a specific problem in a specific location, like a runny nose or

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sore throat, while antineoplastic drugs target all unhealthy cells
in a person's body.

The problem with this is that it is very hard to design a drug to

kill only cancer cells that won't accidentally harm other cells at
the same time. They work in a way that is similar to the weed
killers that you use to kill unwanted plants that might be
growing in your grass.

The weed killer will definitely kill the weeds, but there is also a
very good chance it will also kill any grass that it gets sprayed
on that might be in the vicinity of the weed.

Antineoplastic drugs are very good at killing their targeted

cells, but a lot of other healthy cells tend to end up as collateral
damage. This lack of specificity is what causes antineoplastic
drugs to have so many potential side effects.

Potential Side Effects

Most people are aware that when people are being treated for
cancer, their treatment often has side effects like hair loss or
weight loss. A side effect is anything experienced by the
human body that is caused by a drug other than what the drug
was designed to do.

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So if you get an upset stomach from taking a medication for
your headache, that upset stomach would be a side effect. It is
a problem that is created when you take a medication to treat a
different problem.

Antineoplastic Drug

Capecitabine

Capecitabine, sold under the brand name Xeloda among

others, is a chemotherapy medication used to treat breast
cancer, gastric cancer and colorectal cancer. For breast
cancer it is often used together with docetaxel. It is taken by
mouth.

Common side effects include abdominal pain, vomiting,

diarrhea, weakness, and rashes. Other severe side effects
include blood clotting problems, allergic reactions, heart
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problems, and low blood cell counts. It is not recommended in
people with kidney problems. Use during pregnancy may result
in harm to the baby. Capecitabine, inside the body, is
converted to 5-fluorouracil (5-FU) through which it acts.

Simple determination of capecitabine and its

metabolites by liquid chromatography with ultraviolet
detection in a single injection
Capecitabine (N4-pentoxycarbonyl-5′-deoxy-5-fluorocytidine,
Xeloda®), a prodrug of 5-fluorouracil (5-FU), is an oral tumor-
selective fluoropyrimidine carbamate approved in the treatment
of colorectal and breast cancer. It has a preferential activation
to 5-FU by thymidine phosphorilase (TP) in target tumor
tissues through a series of three metabolic steps minimizing
the exposure of normal tissues to 5-FU. It offers the potential
of less gastrointestinal toxicity and advantages in terms of
convenience and quality of life for the patient, in addition to
cost-effectiveness as compared with intravenous 5-FU
chemotherapy. We developed a high performance liquid
chromatography assay for the determination of plasma
capecitabine and its nucleoside metabolite concentrations and
5-FU catabolite dihydro-5-fluorouracil in a single step
extraction and a single HPLC injection. The retention times of
dihydro-5-fluorouracil, 5-FU, 5′-deoxy-5-fluorouridine (5′-
DFUR) and capecitabine were 3.6, 4.4, 11.4 and 20.4 min,

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respectively and the internal standard retention times were 8.7
and 12.2 min for 5-bromouracil (5-BU) and tegafur,
respectively. The limit of detection was 0.01 μg/ml for
capecitabine and its nucleoside metabolites and the limit of
quantification was 0.025 μg/ml. Extraction efficiency was >80%
with a single solvent mixture extraction step for all analytes of
interest. The assay had good precision, the within-day and
between-day standard deviation of the mean (R.S.D.) being
<10% in the linear range 0.025–10 μg/ml. The authors
conclude that the method described here is ideally suited for
the therapeutic monitoring of capecitabine and its metabolites.

Rapid and simultaneous determination of capecitabine

and its metabolites in mouse plasma, mouse serum,
and in rabbit bile by high-performance liquid
chromatography.

A rapid high-performance liquid chromatography method has

been developed for simultaneous determination of
capecitabine and its metabolites: 5'-deoxy-5-fluorocytidine (5'-
DFCR), 5'-deoxy-5-fluorouridine (5'-DFUR) and 5-fluorouracil
(5-FU). 5'-DFCR was synthesized by hydrolyzing capecitabine
using commercially available carboxyl esterase (CES) and
characterized by NMR, mass spectrometry and elemental
analysis. Base-line separations between capecitabine, 5'-
DFCR, 5'-DFUR and 5-FU were found with symmetrical peak

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shapes on a Discovery RP-amide C16 column using 10 mM
ammonium acetate at pH 4.0 and methanol as the mobile
phase. The retention times of capecitabine, 5'-DFCR, 5'-DFUR
and 5-FU were 8.9, 5.0, 5.3 and 3.0 min, respectively. Linear
calibration curves were obtained for each compound across a
range from 1 to 500 microg ml(-1). The intra- and inter-day
relative standard deviations (%RSD) were <5%. A single-step
protein precipitation method was employed for separation of
the analytes from bio-matrices. Greater than 85% recoveries
were obtained for capecitabine, 5'-DFCR, 5'-DFUR and 5-FU
from bio-fluids including mouse plasma, mouse serum and
rabbit bile.

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