Determination of the rifamycin antibiotics rifabutin, rifampin, rifapentine and their major metabolites in human plasma via simultaneous extraction coupled with LC/MS/MS

摘要

A novel assay using high pressure liquid chromatography (HPLC) coupled to mass spectrometer (MS) detection was developed and validated for the rifamycin anti-tuberculosis antibiotics rifampicin (RIF), rifabutin (RBT), rifapentine (RPT) and their active desacetyl metabolites (dRIF, dRBT and dRPT, respectively) in human plasma. The assay uses 50 mu L of human plasma with a quick and simple protein-precipitation extraction to achieve a dynamic range of 75-30,000 ng/mL for RIF, RBT and RPT and 37.5-15,000 ng/mL for dRIF, dRBT and dRPT, respectively. The average %CV and %deviation were less than 20% at the lower limit of quantitation and less than 15% over the range of the curve. The method was fully validated according to FDA criteria for bioanalytical assays and has successfully been used to support three large international tuberculosis trials. (C) 2014 Elsevier B.V. All rights reserved.