Stability indicating HPTLC determination of clopidogrel bisulphate as bulk drug and in pharmaceutical dosage form Himani Agrawal, Neeraj Kaul, A.R. Paradkar, K.R. Mahadik * Department of Quality Assurance Techniques, Bharati Vidyapeeth Deemed University, Poona College of Pharmacy, Erandwane, Pune 411038, Maharashtra State, India Received 27 March 2003; received in revised form 5 May 2003; accepted 5 May 2003 Abstract A sensitive, selective, precise and stability indicating high-performance thin layer chromatographic method of analysis of clopidogrel bisulphate both as a bulk drug and in formulations was developed and validated in pharmaceutical dosage form. The method employed TLC aluminium plates precoated with silica gel 60F-254 as the stationary phase. The solvent system consisted of carbon tetrachloride  /chloroform  /acetone (6:4:0.15, v/v/v). This system was found to give compact spots for clopidogrel bisulphate (R f value of 0.309 /0.01). Clopidogrel bisulphate was subjected to acid and alkali hydrolysis, oxidation, photodegradation and dry heat treatment. Also the degraded products were well separated from the pure drug. Densitometric analysis of clopidogrel bisulphate was carried out in the absorbance mode at 230 nm. The linear regression data for the calibration plots showed good linear relationship with r 2 /0.9999 /0.001 in the concentration range of 200  /1000 ng. The mean value of correlation coefficient, slope and intercept were 0.9999 /0.001, 0.0939 /0.011 and 8.839 /0.99, respectively. The method was validated for precision, accuracy, ruggedness and recovery. The limits of detection and quantitation were 40 and 120 ng per spot, respectively. The drug undergoes degradation under acidic and basic conditions, oxidation and dry heat treatment. All the peaks of degraded product were resolved from the standard drug with significantly different R f values. This indicates that the drug is susceptible to acid  /base hydrolysis, oxidation and dry heat degradation. Statistical analysis proves that the method is reproducible and selective for the estimation of the said drug. As the method could effectively separate the drug from its degradation products, it can be employed as a stability indicating one. # 2003 Elsevier B.V. All rights reserved. Keywords: Clopidogrel bisulphate; High-performance thin layer chromatography; Stability indicating; Degradation 1. Introduction Clopidogrel hydrogen sulphate, methyl ( /)-(S )- (o -chlorophenyl)-6,7 dihydrothieno[3,2-c]pyridin- 5(4H)-acetate hydrogensulphate (Fig. 1) is a new thienopyridine derivative chemically related to ticlodipine. It has been shown to prevent ischaemic * Corresponding author. Tel.:  /91-20-543-6898; fax:  /91- 20-543-9383. E-mail address: krmahadik@rediffmail.com (K.R. Mahadik). Talanta 61 (2003) 581  /589 www.elsevier.com/locate/talanta 0039-9140/03/$ - see front matter # 2003 Elsevier B.V. All rights reserved. doi:10.1016/S0039-9140(03)00364-3