Bioanalytical method development and validation of different drugs by using LC-MS/MS

Abstract

The work presented in this thesis includes selective, sensitive and first automated LC-MS/MS method[s] development, validation and their application[s] for simultaneous quantification of drug[s] and their metabolite[s] in human plasma. newlineThese developed and validated methods are accurate, precise and robust for the molecules such as aceclofenac, artemether, alverine and its metabolite p-hydroxy alverine, clopidogrel and its carboxylic acid metabolite [on HTLC-MS/MS], carvedilol and its metabolite 4-Hydroxyphenyl Carvedilol [on HTLC-MS/MS], clonidine, lumefantrine, levetiracetam, telmisartan and ursodeoxycholic acid. newlineThe precision and accuracy data gives a result, which were within the acceptance limits. Consistent recoveries were observed. The method is specific in the presence of different anticoagulants [CPDA and EDTA] and matrices collected from different sources. The desired sensitivity was achieved with an LLOQ, which has within- and between-batch coefficients of variance [CVs], respectively. newlineElectrospray ionization technique has proven effective in generating ions close to the protonated molecule with sufficient intensity to monitor quantitatively, accurately and selectively. newlineThe methods by the author are being successfully employed to quantify the drugs and their metabolites in human plasma for bioavailability and bioequivalence studies. newlineThe current methods include a simple and rapid sample preparation as a result of robotic systems utilization that enabled parallel processing with small amounts of solvents and biological fluids for extraction as well as significantly shorter analysis run time and potential to replace the less accurate, time-consuming, labour-intensive conventional methods for routine analysis.