Quantitative determination of abacavir (1592U89), a novel nucleoside reverse transcriptase inhibitor, in human plasma using isocratic reversed-phase high-performance liquid chromatography with ultraviolet detection

Abacavir is a novel nucleoside reverse transcriptase inhibitor for the trea tment of HIV-1 infection. A simple and rapid high-performance liquid chroma tographic method for the quantification of abacavir in human plasma suitabl e for pharmacokinetic research purposes is described. Sample pretreatment c onsists of protein precipitation with perchloric acid. The supernatant is i njected directly into the chromatographic system after centrifugation. The drug is separated from endogenous compounds by isocratic reversed-phase hig h-performance liquid chromatography with ultraviolet detection at 285 nm. T he method has been validated over the range of 20-2000 ng/ml using a volume of 300 mu l of plasma. The assay is linear over this concentration range a s indicated by the F-test for lack-of-fit. Within- and between-day precisio ns are less than 7.5% for all quality control samples. The lower limit of q uantitation is 20 ng/ml and the recovery of abacavir is 88.1% (+/-1.3%). Fr equently coadministered drugs did not interfere with the described methodol ogy. Abacavir is stable in human plasma under various relevant storage cond itions, for example when stored for 51 days at -20 degrees C. This validate d assay is suited for use in pharmacokinetic studies with abacavir in human plasma and can readily be implemented in the setting of a hospital laborat ory for the monitoring of abacavir concentrations. (C) 1999 Elsevier Scienc e B.V. All rights reserved.