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Please use this identifier to cite or link to this item: http://hdl.handle.net/123456789/3137

Title: STRESS DECOMPOSITION STUDIES AND DEVELOPMENT OF VALIDATED STABILITY INDICATING HPLC ASSAY METHOD FOR LAMIVUDINE
Authors: Berrhanue Muche
Advisors: Prof. Tsige Gebre-Mariam
Dr.Kalab Assress
Keywords: Lamivudine
HPLC
SIAMs
Copyright: Jul-2005
Date Added: 22-May-2012
Publisher: ADDIS ABABA UNIVERSITY
Abstract: Lamivudine belongs to the class of nucleoside reverse transcriptase inhibitors, and is potent in vitro and in vivo inhibitors of human immunodeficiency virus (HIV), which is the causative agent of the acquired immunodeficiency syndrome. Various analytical methods have been reported for the determination of lamivudine in the biological fluid such as plasma, CSF, saliva and urine. They have been used to support pharmacokinetic study. However, there are no reported stability-indicating HPLC assay methods for this drug. Though reported methods are highly specific and sensitive for this drug they may not yield precise and accurate result for determination of the API in the presences of its degradation product. Stability requirements for the world wide registrations of pharmaceutical products have undergone a dramatic change in the past few years with the advent of ICH guidelines. ICH has introduced a standardized approach for the development of stability data for registration through various guidelines. Therefore, it is necessary to develop a stability indicating method for these drugs to ensure the safety, quality and efficacy of these drugs. The aim of the present study is thus to establish the inherent stability of lamivudine, a nucleoside reverse transcriptase inhibitor, through stress studies under a variety of ICH recommended test conditions and develop validated stability indicating assay method. In this study all solution was prepared and used according to USP 24 and BP 1999 and forced decomposition studies were conduct to generate degradation products of the API following the condition recommended by the ICH guideline Q1A. The stressed samples obtained were subjected to preliminary analyses by employing HPLC to study the number and types of degradation products formed under various conditions. The result of this study showed that the drug was liable to degradation in all stressed condition though the extent of degradation varied. The API was found to be more liable to decompositions in alkaline solution than in acidic solution and neutral condition. Degradation of lamivudine in neutral solution was observed relatively after long hour of refluxing indicating that the drug is relatively stable in neutral condition. Relative rate of degradation of the drug in hydrolytic and oxidative condition shows that the rate of hydrolytic degradation in xiii acidic solution (0.1N HCl) was less than the rate of oxidative degradation in hydrogen peroxide (3.0%). Separation of the drug and the degradation products under various conditions was successfully achieved on C-8 column by using a mobile phase composed of 0.1M ammonium acetate: methanol: 1 %(v/v) acetic acid in the ratio of 91.9:8:0.1. The method was validated with respect to linearity, precision, accuracy, selectivity, specificity and ruggedness. The response was linear (r=0.9998) in the drug concentration range of 5-500 μgml-1. The mean values (±RSD) of slope and intercept were 46376 (±0.006975) and 200049 (±0.4009) respectively. The RSD values for intra–and inter-day precision studies were <0.292 %and <1.781% respectively. The recovery of the drug ranged between 98.3 - 101.16% from the mixture of degradation products. The method was specific to the drug and also selective to degradation products. The developed method is simple accurate, precise, specific and selective and rugged and thus it can be used for analysis of the drug and its degradation products.
URI: http://hdl.handle.net/123456789/3137
Appears in:Thesis - Pharmaceutical Analysis & Quality Assurance

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