ISSN print edition: 0366-6352 ISSN electronic edition: 1336-9075 Registr. No.: MK SR 9/7 Published monthly

Validated chiral chromatographic methods for clopidogrel bisulphate and its related substances in bulk drug and pharmaceutical dosage forms

Eman S. Elzanfaly, Hala E. Zaazaa, Aya T. Soudi, and Maissa Y. Salem

Analytical Chemistry Department, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo 11562, Egypt

E-mail: aya.soudi@pharma.cu.edu.eg

Abstract: Two validated chromatographic methods developed for the analysis of S clopidogrel bisulphate in the presence of its related substances listed in the United States and British Pharmacopoeias including its inactive R enantiomer are described. The first method is a simple thin layer chromatographic (TLC) method where separation is performed on pre-coated silica gel 60 F254 plates using methanol/diethylamine/heptanes/water containing 20 mg vancomycin hydrochloride (7 : 7 : 1.5 : 0.5 vol. %) as a mobile phase. R_f values were found to be 0.69, 0.74, 0.78, 0.84 and 0.88 for R clopidogrel, S clopidogrel, related substances A, B1 and B2, respectively. The second method depends on the separation by HPLC on a Lux polysaccharide chiral column with UV detection at 220 nm using 0.1 vol. % diethyl amine in methanol pumped at a rate of 1 mL min⁻¹. Retention times were found to be 1.90 min, 2.82 min, 3.00 min, 3.27 min and 3.71 min for the related substances A, B1, C which are clopidogrel R enantiomer, B2, and S clopidogrel, respectively. The proposed methods were validated in accordance with the ICH guidelines and successfully applied to the determination of S clopidogrel bisulphate in pure powder and dosage forms without interference from the excipients and to affirm the dosage form to be pure S clopidogrel and devoid of the R enantiomer, which is inactive.

Keywords: HPLC – TLC densitometry – S clopidogrel – R clopidogrel – related substances – chiral separation

Full paper is available at www.springerlink.com.

DOI: 10.1515/chempap-2015-0179

Chemical Papers 69 (12) 1541–1547 (2015)