Stress Decomposition Studies And Development Of Validated Stability Indicating Hplc Assay Method For Lamivudine

Lamivudine belongs to the class of nucleoside reverse transcriptase inhibitors, and is potent inrnvitro and in vivo inhibitors of human immunodeficiency virus (HIV), which is the causativernagent of the acquired immunodeficiency syndrome. Various analytical methods have beenrnreported for the determination of lamivudine in the biological fluid such as plasma, CSF,rnsaliva and urine. They have been used to support pharmacokinetic study. However, there arernno reported stability-indicating HPLC assay methods for this drug. Though reported methodsrnare highly specific and sensitive for this drug they may not yield precise and accurate resultrnfor determination of the API in the presences of its degradation product. Stabilityrnrequirements for the world wide registrations of pharmaceutical products have undergone arndramatic change in the past few years with the advent of ICH guidelines. ICH has introducedrna standardized approach for the development of stability data for registration through variousrnguidelines. Therefore, it is necessary to develop a stability indicating method for these drugsrnto ensure the safety, quality and efficacy of these drugs.rnThe aim of the present study is thus to establish the inherent stability of lamivudine, arnnucleoside reverse transcriptase inhibitor, through stress studies under a variety of ICHrnrecommended test conditions and develop validated stability indicating assay method.rnIn this study all solution was prepared and used according to USP 24 and BP 1999 and forcedrndecomposition studies were conduct to generate degradation products of the API followingrnthe condition recommended by the ICH guideline Q1A. The stressed samples obtained werernsubjected to preliminary analyses by employing HPLC to study the number and types ofrndegradation products formed under various conditions.rnThe result of this study showed that the drug was liable to degradation in all stressedrncondition though the extent of degradation varied. The API was found to be more liable torndecompositions in alkaline solution than in acidic solution and neutral condition. Degradationrnof lamivudine in neutral solution was observed relatively after long hour of refluxingrnindicating that the drug is relatively stable in neutral condition. Relative rate of degradation ofrnthe drug in hydrolytic and oxidative condition shows that the rate of hydrolytic degradation inrnxiiirnacidic solution (0.1N HCl) was less than the rate of oxidative degradation in hydrogenrnperoxide (3.0%). Separation of the drug and the degradation products under variousrnconditions was successfully achieved on C-8 column by using a mobile phase composed ofrn0.1M ammonium acetate: methanol: 1 %(v/v) acetic acid in the ratio of 91.9:8:0.1. Thernmethod was validated with respect to linearity, precision, accuracy, selectivity, specificity andrnruggedness. The response was linear (r=0.9998) in the drug concentration range of 5-500rnμgml-1. The mean values (±RSD) of slope and intercept were 46376 (±0.006975) and 200049rn(±0.4009) respectively. The RSD values for intra–and inter-day precision studies were

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