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Aboul-Enein2* and Şerban Fleschin3
CROMATEC_PLUS SRL, Analytical Research Department, 18 Sos. Cotroceni, Bucharest - 6, 060114, Romania. College of Pharmacy, University of Sharjah, P.O.Box 27272 , Sharjah, United Arab Emirates. 3 Department of Analytical Chemistry, Faculty of Chemistry, University of Bucharest, 92-96, Sos. Panduri, Bucharest5, 050663, Romania.
Received: April 28, 2006
Accepted (in revised form): July 5, 2006
Abstract A Fourier transform infrared (FT-IR) spectrometric method was developed for the rapid, direct measurement of acetylsalicylic acid (ASA) in different pharmaceutical products. Conventional KBr-spectra spectra were compared for the best determination of active substance in drug preparations. The Beer-Lambert law and two chemometric approaches, partial least squares (PLS) and principal component regression (PCR+) methods, were used in data processing. Keywords: FT-IR analysis, acetylsalicylic acid, drug analysis, calibration curve, chemometric approaches Résumé Nous avons développé une méthode de spectrométrie infrarouge transformée de Fourier (FT-IR) pour la mesure rapide et directe de l’acide acétylsalicylique (ASA) dans différents produits pharmaceutiques. Les spectres KBr conventionnels ont été comparés pour une meilleure détermination de la substance active dans la préparation des médicaments. La loi de Lambert-Beer et deux approches chémométriques, la méthode des moindres carrés partiels (PLS) et celle de la composante de régression principale (PCR+) ont servi au traitement des données.
Introduction Infrared spectrometry (IR) provides a useful way for the identiﬁcation of drugs (1-4). However, the traditional techniques employed to obtain the IR spectra, such as alkali halides disks, mulls and thin ﬁlms, are sometimes not adequate for quantitative analysis. Fourier Transform (FT-IR) permits continuous monitoring of the spectral baseline and simultaneous analysis of different components of the same sample (5,6). Acetylsalicylic acid (ASA, o-acetoxybenzoic acid, aspirin ) (see Figure 1) is one of the oldest analgetics substance. Already Hippocrates (460-370 B.C.) used an extract of bark of willow trees – containing a high quantity of salicylic acid to relieve pain (7). Aspirin is used to relieve mild to moderate pain, reduce fever, redness, and swelling, and to help prevent blood from clotting. It is used to relieve discomfort caused by numerous medical problems, including headaches, infections, and arthritis. It is also used to reduce the risk of a second heart attack or stroke. Larger doses of aspirin are used to treat gout. Acetylsalicylic acid inhibits the body’s pro-
* Author to whom correspondence should be addressed: e-mail: Professor H.Y. Aboul-Enein (firstname.lastname@example.org)
Figure 1. Structure of acetylsalicylic acid. Canadian Journal of Analytical Sciences and Spectroscopy
and from Europharm Braşov Romania (sample C). (sample A). respectively.0 mg. The commercial softwares used to generate analysis for the principal component analysis were QUANT+ expert v. while the background was spectral grade KBr (ASA_KBr). In PCR and PLS2. ASA. In order to compress the sample against the crystal. USA. PLS) method is given by Geladi and Kowalski (15). A good introduction to the partial least squares (Projection to Latent Structures..0 mg of drug sample with spectral grade KBr. respectively) were compared and recommendations for the best options in ASA analysis were made. (0. Inc. a pressure plate and clamp are provided. 5.2. Chemometric methods. No. the spectra are modeled by one duction of prostaglandins. 1. the spectra were recorded with the same detector from samples prepared by compressing the standard substance. The purpose of the present study is to investigate the potential of FT-IR spectrometry to quantify ASA in pharmaceutical preparations.0 mg. Chemometric techniques which are known as numerical techniques are useful for the spectrophotometric resolution of complex mixtures of analytes without the need of prior separation or extraction. fever. For calibration. Improved Principal Component Regression. respectively. The main objective of this work was to develop a chemometric procedure for the fast and accurate determination of ASA in commercial pharmaceutical formulations by using the Beer-Lambert law and/or PCR+ and PLS approaches. and partial least squares (PLS2. The pharmaceuticals were manufactured by Bristol – Myers Squibb Egypt a Bristol-Myers Squibb Company (New York. and Şerban Fleschin (Perkin Elmer Co. PLS1.. CA. such as principal component regression (PCR+). Prostaglandins are hormonelike substances which are involved in the regulations of varied processes such as pain. The techniques described for the assay of ASA are high performance liquid chromatography (8). Prostaglandins elicit signals of pain and so by obstructing their synthesis. These two techniques yields more accurate calibration models compared with multiple linear regression (MLR) where a restricted set of absorption bands is used in the calibration. by averaging 32 scans for each spectrum with a Spectrum 100 Universal Diamond/ZnSe ATR with 3 Reﬂection Top-Plate (ASA_UATR). respectively) in spectral grade KBr. Reagents and materials Acetylsalicylic acid was provided by Leiner Healt Prod. Beaconsﬁeld.5.254 Andrei A. inﬂammations and thromboses. Recommended procedures Conventional fused KBr disk spectra were recorded between 4000 and 350 cm-1. The universal ATR spectra were recorded between 4000 and 650 cm-1. UK). respectively. Carson. from RAMEDA (The Tenth of Ramadan) Co. The determination of the major components in drugs with FT-IR spectrometry provides an enormous amount of spectroscopic information of a sample. PLS2 or the Beer-Lambert law. 2006 . The proposed analytical method in this study was performed on standard ASA and three different aspirin containing pharmaceutical formulations namely BUFFERIN .51 and Spectrum Beer’s law v.01 (Perkin Elmer Co. by averaging 64 scans for each spectrum with a resolution of 4 cm-1 (data point resolution/interval cm-1) with a DTGS detector from samples prepared by compressing 2. Bunaciu.01 Volume 51.sample A containing about 325 mg of ASA per tablet. Experimental Apparatus Data acquisition was performed using a Spectrum100 Systems FT-IR spectrometer equipped with Spectrum for Windows v. 1. no pain can be felt. reducing the sample pre-treatment and providing direct FTIR measurement.5 mg. Although both PCR and PLS give succesuful results.4. and other techniques relying spectrophotometry (9-12) or capillary electrophoresis techniques (13). Multicomponent Partial Least Squares) analysis are commonly used to extract the speciﬁc information relevant to the analyte of interest from the full spectrum (1.Cairo).5 mg and 2.sample B containing about 75 mg of ASA per tablet and EUROPIRIN T . Aboul-Enein. AGGREX . Results and Discussion Figures 2-5 present spectra of standard acetylsalicylic acid as well as for the pharmaceutical preparations using the KBr disk method and UATR. Experimental parameters and calibration methods (PCR+. Egypt (sample B). Bucks. they have several disadvantages such as using abstract mathematical theory and various softwares. UK).sample C containing about 500 mg of ASA per tablet. 14). It is of interest to note that there are no signiﬁcant differences in the ﬁngerprinting region between the spectra obtained from the KBr disk and UATR methods. Hassan Y.
FT-IR spectra of ASA standard using the UATR method. FT-IR spectra of ASA standard using the KBr-disk method. Canadian Journal of Analytical Sciences and Spectroscopy .2.FT-IR Spectrophotometric analysis of acetylsalicylic acid and its pharmaceutical formulations 255 Fig. Figure 3.
Bufferin 325mg ASA per tablet. Aboul-Enein. Europirin 500mg ASA per tablet. Aggrex 75 mg ASA per tablet. c. FT-IR spectra of pharmaceutical preparations containing ASA using the KBr-disk. Hassan Y. Volume 51. Aggrex 75 mg ASA per tablet. No. b. and Şerban Fleschin Figure 4.256 Andrei A. b. Europirin 500mg ASA per tablet. FT-IR spectra of pharmaceutical preparations containing ASA using the UATR method. Figure 5. Bufferin 325mg ASA per tablet. Bunaciu. a. 2006 . a. c. 5.
Calibration curve according to the Beer-Lambert law for the quantitative determination of ASA in pharmaceutical preparations. .FT-IR Spectrophotometric analysis of acetylsalicylic acid and its pharmaceutical formulations 257 Canadian Journal of Analytical Sciences and Spectroscopy Figure 6.
35 Sample C Content (mg/tablet) RSD (%) (n = 5) Slope Intercept Correlation coefﬁcient ASA_KBr 487.85 2.55 3.2048A 0.88 3.3572A 0. Comparison of the ASA determination in tablets obtained by FT-IR and the Beer-Lambert law methods.892 310.2189A 0. No.11 ASA_UATR 70.06929A 0.03 2.258 Andrei A. Sample A ASA_KBr PCR+ RMS Error Peak-to-Peak Error Total M-Distance Content (mg/tablet) RSD (%) (n = 5) 0.25 Sample B Content (mg/tablet) RSD (%) (n = 5) ASA_KBr 72.1949A 0.925 480.14 Calibration parameters 15.1928A 0.99 Table 1.34 2.5100 -1.2123 0.2088A 0. 5.15 2.01 PCR+ 0.12 2.9322A 0.9886 ASA_UATR 477. Table 2.58 4.61 4.15 ASA_KBr PCR+ RMS Error Peak-to-Peak Error Total M-Distance Content (mg/tablet) RSD (%) (n = 5) 0. 2006 ASA_UATR PLS 0.34 3.978 476.99 .87 PLS 0.2019A 0.798 68.07 Sample B ASA_UATR PLS 0.26 3. Comparision of the ASA determination in tablets using the FT-IR chemometric approaches.93 0.1878A 0.09019A 0.884 483.9545A 0.68 2.3359A 0.07863A 0.45 ASA_KBr PCR+ RMS Error Peak-to-Peak Error Total M-Distance Content (mg/tablet) RSD (%) (n = 5) Volume 51.99 PLS 0.38 3.848 71.8977A 0. Bunaciu.953 315.967 316. and Şerban Fleschin Sample A Content (mg/tablet) RSD (%) (n = 5) ASA_KBr 318.4232A 0.87 2.2023A 0.07129A 0.18 Sample C ASA_UATR PLS 0.59 1. Aboul-Enein.9322A 0. Hassan Y.24 3.9722A 0.910 478.97 2.25 2.927 312.05 ASA_UATR 312.04 PCR+ 0.8637A 0.17 PCR+ 0.3312A 0.8729A 0.85 PLS 0.9022A 0.952 70.929 69.
pp.9886. Carducci. Poppi. Convection Inc. Fatmi and G. Anal. Dinç. J. London. the method proposed is simple. E. Biomed. the results are very similar. Rockville.. Analyst. (sample A).. 809.W. 185. p. provide a typical calibration line which corresponds to: A = .M. E. precise and not time-consuming compared to the chromatographic methods that exist in literature. 35. ed..0%). pp.L. 35. 11. Romania (sample C).. V. Pharm. 1990. E. respectively. We studied the possibility to use the Beer-Lambert law for the quantitative determination of ASA in pharmaceutical products at 1605. and Kowalski.FT-IR Spectrophotometric analysis of acetylsalicylic acid and its pharmaceutical formulations set of factors and each property is modeled by relating the concentration values to those factors.E. Baleanu. F. Marcel Dekker. Özdemir and D. Baleanu. Garrigues. 1986. 1849 (1992). III. eds. Inc. de la Guardia. M. A. M. Anal. A. because of the smaller value of RSD (< 3.R. As can be seen in Table 1 and 2. J. David F. Chromatogr. Wold. 1992. 27 (1994). Anal. Liq. Lucangioli. P. Egypt (sample B). Marcel Dekker. 4. Canadian Journal of Analytical Sciences and Spectroscopy . Talanta. Silvia Paasch and Reiner Salzer. and from Europharm. 27 (1999). 12. W.. 15. Burns.). The Pharmaceutical Society of Great Britain. Molina. in Handbook of Near-Infrared Analysis. 5 (2004). J. Anal.. 6. while Tables 1 and 2 show the results obtained by Beer’s law method and chemometric approaches.E.. Hence. M... 380. 545 (2002). Cordova and A. 1966. Dinç. With the commercial software involving chemometric approaches. Gallignani. and Ciurczak.J. Danielson.Chim.R. Capillary Electrophor.F. 9.Rodriguez.A. 2. R. 181-274.C. Sena and R. 983 (2002).E. Onur and D. The measurements. S. Figure 6 presents the calibration curve for ASA using the KBr disk method.D. New York. 3. including sample preparation and spectral acquisition. (ed. 10. Spectrosc. 2001.D. Pharmaceutical and Medical Applications of Near-Infrared Spectroscopy.49 cm-1. the spectra are modeled by a different set of factors for each property and the concentration values are modeled by the respective factors. A. USP XXII (United States Pharmacopoeia. 12 . S.. 14. 401(1988).G. B and C represents the pharmaceuticals formulations manufactured by Bristol – Myers Squibb Egypt.2132 + 15. Beer-Lambert law. and M. J.. Inc. In PLS1. Biochem. Research Papers in Statistics. Quantiﬁcation could be done in about 5-10 minutes.. H.1.V. B. 13.. Acta.51 C(mg ASA) with a regression coefﬁcient. New York. and Katon. 36 (2005).. J. Moffat A. Chem. 10. and Drennen. 21. where A.. carried out by the above mentioned conditions. FernandezOtero. 73-105. B. Pharm. 1 (1986). Lett. Williams. 8. Acknowledgements One of the authors (AAB) wishes to thank the Administration of CROMATEC_PLUS SRL for the ﬁnancial support. of 0..N. 22nd revision). 65. 7. 5. 2nd Ed.F. McClure. Anal. and we suggest the use of the PCR+ method. Analysis Using Fourier Fransforms. MD. Ciurczak. 2461 (1987).N. D.Vizioli and C. Appl. Clarke’s Isolation and Identiﬁcation of Drugs. N.C. New York. E.. A. Medina. where n is the number of properties in the method. Biomed. Geladi. 1990. PLS1 really contains n separate calibrations.M. N. G.. Miller.. 117. References 259 1. from RAMEDA Co. Conclusions It is clear that FT-IR spectrometry is capable of direct determination of ASA in several formulations. J.. Wiley.K. 42.W.
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