Abstract

COMPARATIVE DEGRADATION KINETIC STUDY OF ESTER LINKAGE OF ANTIPLATELET AGENT CLOPIDOGREL UNDER ALKALINE STRESS CONDITION BY CONVENTIONAL METHOD THROUGH ACID HYDROLYSIS BY MICROWAVE AND BY RP-HPLC

Kamlesh R. Prajapati*, Sneh N. Patel and Prof. Dr. Dhrubo Jyoti Sen

ABSTRACT

A simple, precise and accurate isocratic RP–HPLC method was developed. The method has shown adequate separation for Clopidogrel and degradation products. Separation was achieved on a Waters C18 (250 mm×4.6 mm i.d., 5 μm particle size) column using a mobile phase consisting of Acetonitrile – Water (80:20 v/v) at flow rate of 1 mL/min and UV detection at 240 nm. This drug was subjected to acid hydrolysis and alkali hydrolysis apply stress conditions.The linearity was investigated in the range of 40–120 μg/mL (r2 = 0.9999) for Clopidogrel. The intraday and interday % RSD values were less than 0.2 %. The LOD and LOQ were 0.1194 μg/mL and 0.3618 μg/mL. Clopidogrel was degraded in acid (1N HCl by Microwave) and alkali (1N NaOH) in different temperature conditions. Clopidogrel was more degraded in alkaline condition compared to acidic. For the degradation kinetic in acidic and alkaline conditions the best fit was obtained for first−order reaction rate. The rate constant (k) is in the alkaline medium, 0.0092 min−1 for 400C NaOH, 0.0455 min−1 for 600C NaOH, 0.4690 min−1 for 800C NaOH and in acid medium 0.1083 min−1 by Microwave. The t1/2 was found to be less in alkaline condition compared to acidic conditions which shows, the drug has lower stability in alkaline medium. The t1/2 for alkaline condition was 75.32 mins at 400C, 15.23 mins at 600C and 1.477 mins at 800C. The t1/2 for acidic condition was 6.39 mins.The activation energy of Clopidogrel in alkaline medium was found to be 3.9174 KJ/mole.

Keywords: Clopidogrel, Rate constant, Microwave, RP – HPLC.