TY - JOUR
T1 - Development and validation of an assay for the simultaneous determination of zidovudine, abacavir, emtricitabine, lamivudine, tenofovir and ribavirin in human plasma using liquid chromatography-tandem mass spectrometry
AU - Pereira, Sofia de Azeredo Gaspar
PY - 2013/1/1
Y1 - 2013/1/1
N2 - This paper describes the development and validation of an assay for the simultaneous quantification of the antiviral and antiretroviral drugs zidovudine, abacavir, emtricitabine, lamivudine, tenofovir and ribavirin in human plasma using liquid chromatography coupled to tandem mass spectrometry. Sample pretreatment consisted of protein precipitation with 0.1\% (v/v) formic acid in methanol, evaporation and reconstitution. Chromatographic separation was performed on a Synergy Polar reversed phase C18 column (150 mm x 2.0 mm ID, particle size 4 mu m) using a stepwise gradient with 0.1\% (v/v) formic acid in water and 0.1\% (v/v) formic acid in methanol at a flow rate of 300 mu L/min. A triple quadrupole mass spectrometer operating in the positive ionization mode was used for drug detection and quantification. Isotopically labeled zidovudine, lamivudine, tenofovir and ribavirin were used as internal standards. The method was validated over a clinical range of 20-2500 ng/mL for zidovudine, lamivudine and tenofovir, 4-500 ng/mL for abacavir and emtricitabine and 160-20,000 ng/mL for ribavirin. The inter and intra-assay accuracies and precisions were between -8.47\% and 14.2\% for zidovudine, emtricitabine and ribavirin. For abacavir, lamivudine and tenofovir, the inter and intra-assay accuracies and precisions at the lower limit of quantification were between -11.0\% and 18.3\%, whereas at all other levels these accuracies and precisions were between -11.7\% and 12.0\%. The described method is suitable for the determination of zidovudine, abacavir, emtricitabine, lamivudine, tenofovir and ribavirin in human plasma in clinical practice to monitor plasma concentrations in selected cases to optimize therapy. (C) 2013 Published by Elsevier B.V.
AB - This paper describes the development and validation of an assay for the simultaneous quantification of the antiviral and antiretroviral drugs zidovudine, abacavir, emtricitabine, lamivudine, tenofovir and ribavirin in human plasma using liquid chromatography coupled to tandem mass spectrometry. Sample pretreatment consisted of protein precipitation with 0.1\% (v/v) formic acid in methanol, evaporation and reconstitution. Chromatographic separation was performed on a Synergy Polar reversed phase C18 column (150 mm x 2.0 mm ID, particle size 4 mu m) using a stepwise gradient with 0.1\% (v/v) formic acid in water and 0.1\% (v/v) formic acid in methanol at a flow rate of 300 mu L/min. A triple quadrupole mass spectrometer operating in the positive ionization mode was used for drug detection and quantification. Isotopically labeled zidovudine, lamivudine, tenofovir and ribavirin were used as internal standards. The method was validated over a clinical range of 20-2500 ng/mL for zidovudine, lamivudine and tenofovir, 4-500 ng/mL for abacavir and emtricitabine and 160-20,000 ng/mL for ribavirin. The inter and intra-assay accuracies and precisions were between -8.47\% and 14.2\% for zidovudine, emtricitabine and ribavirin. For abacavir, lamivudine and tenofovir, the inter and intra-assay accuracies and precisions at the lower limit of quantification were between -11.0\% and 18.3\%, whereas at all other levels these accuracies and precisions were between -11.7\% and 12.0\%. The described method is suitable for the determination of zidovudine, abacavir, emtricitabine, lamivudine, tenofovir and ribavirin in human plasma in clinical practice to monitor plasma concentrations in selected cases to optimize therapy. (C) 2013 Published by Elsevier B.V.
KW - Bioanalysis
KW - NUCLEOSIDE
KW - SEMINAL PLASMA
KW - REVERSE-TRANSCRIPTASE INHIBITORS
KW - PHARMACOKINETICS
KW - LC-MS/MS METHOD
KW - HBV
KW - ANTIRETROVIRAL DRUGS
KW - HIV
KW - HCV
KW - Nucleoside reverse transcriptase inhibitor
KW - Nucleotide reverse transcriptase inhibitor
KW - SIMULTANEOUS QUANTIFICATION
KW - HUMAN SERUM
KW - CHRONIC HEPATITIS-C
KW - STAVUDINE
U2 - 10.1016/j.jchromb.2013.01.005
DO - 10.1016/j.jchromb.2013.01.005
M3 - Article
C2 - 23411018
VL - 919
SP - 43
EP - 51
JO - Journal Of Chromatography B-Analytical Technologies In The Biomedical And L
JF - Journal Of Chromatography B-Analytical Technologies In The Biomedical And L
SN - 1570-0232
IS - NA
ER -