Quality Assessment of Some Commonly Used Enantiomeric Drugs in Bangladesh

Abstract

This thesis describes rapid, accurate, precise, less time consuming analytical methods with excellent resolution for separation and determination of chiral drugs. By performing significant number of trial and error methods using a large number of polar and non-polar solvent mixtures as mobile phase, new and suitable chiral HPLC methods were developed for the separation of common enantiomeric drugs such as omeprazole, esomeprazole, rabeprazole, pantoprazole, salbutamol, levosalbutamol, ibuprofen, dexibuprofen, ofloxacin, levofloxacin, citalopram, Scitalopram,

carvedilol and propranolol which are commonly prescribed in pharmaceutical formulations in Bangladesh. The chiral separation was achieved on different chiral columns, such as, Chiralcel OD-H, Chiralpak AGP, Chiralcel IC, Lux cellulose-3 and Chiral CD-PH (250 x 4.6 mm, 5 µm particle size, Daicel Chemical Industries Ltd., Tokyo, Japan) for various chiral drugs. This thesis presents suitable chiral HPLC methods for the respective drugs which have been validated according to the guidelines of the United States of Pharmacopeia (USP) and International Conference on Harmonization (ICH). For all enantiomeric drugs, the calibration curve showed good linearity with coefficient of determination (r ) values of ≤0.995. The percentage recovery for all drugs was found to be within the limit (97%-103%) and also the percentage of relative standard deviation (%RSD) of repeatability and intermediate precision was within the acceptable limit (%RSD ≤2). It showed that all the proposed methods met the system suitability criteria with resolution (> 2) though it is very difficult to separate enantiomers having similar physical and chemical properties. The limit of detection (LOD) and the limit of quantitation (LOQ) were also evaluated. Others parameters such as, capacity factor and selectivity were also determined for each method. Finally, all methods have been applied for quantitative determination of enantiomers of the respective drugs and calculated percentage purity of enantiomeric drugs. 2 The current research presents the enantiomeric quantitation and purity profiles of the following enantiomeric formulations of different manufacturers of Bangladesh: I. Omeprazole of twenty-six pharmaceutical companies and S-omeprazole (esomeprazole) of twenty-six companies, II. Rabeprazole of sixteen companies, III. Pantoprazole of twenty companies, IV. Salbutamol of ten companies and levosalbutamol of twelve companies, V. Ibuprofen of twelve companies and dexibuprofen of twelve companies, VI. Citalopram of two companies and S-citalopram of nine companies, VII. Ofloxacin of three companies and levofloxacin of nine companies, VIII. Carvedilol of five companies, and IX. Propranolol of six companies.

Thus, all the proposed chiral HPLC methods can be used for routine analysis of the respective drugs for the enantiomeric determination in bulk as well as in pharmaceutical formulations of Bangladesh by simultaneous quantification of (S)- and (R) enantiomers.