SIMULTANEOUS DETERMINATION OF ARTESUNATE AND AMODIAQUINE IN HUMAN PLASMA USING LC-MS/MS AND ITS APPLICATION TO A PHARMACOKINETIC STUDY
Keywords:
Artesunate and amodiaquine, Human plasma, Nil, Method validation, PharmacokineticsAbstract
Objective: The objective of this research was to develop a simple, rapid and sensitive liquid chromatography/tandem mass spectrometry (LC-MS/MS) method for the simultaneous quantification of artesunate and amodiaquine in human plasma.
Methods: An analytical method based on LC-MS/MS has been developed and validated for the simultaneous determination of artesunate and amodiaquine in human plasma. Isotope-labeled compounds are used as internal standards for the quantification of these drugs. Analytes were extracted from the plasma using solid phase extraction (SPE) technique and chromatographed on a C8 column using an isocratic mobile phase composed of 0.1% ammonia solution and methanol (10:90, v/v). The mobile phase was pumped at a flow rate of 1.00 ml/min. A total of five analytical batches were generated for the calculation of intra-day and inter-day precision and accuracy during the entire course of validation.
Results: The assay exhibits excellent linearity in the concentration range of 3.07–305.29 ng/ml for artesunate and 0.30–30.01 ng/ml for amodiaquine. Intra-day and inter-day precision and accuracy results are well within the acceptance limits. All the stability experiments were conducted in plasma samples and in neat samples are complying with the recent US FDA and EMEA guidelines.
Conclusion: The proposed LC–MS/MS assay method is simple, rapid and sensitive enough for the simultaneous determination of artesunate and amodiaquine in human plasma. This method was successfully used to quantitate the in-vivo plasma concentrations obtained from a pharmacokinetic study and the results were validated by conducting incurred samples reanalysis (ISR).
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