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

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Abstract

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.
Original languageUnknown
Pages (from-to)43-51
JournalJournal Of Chromatography B-Analytical Technologies In The Biomedical And L
Volume919
Issue numberNA
DOIs
Publication statusPublished - 1 Jan 2013

Cite this

@article{aaf5fd6934034daeb06e0deb4a8cee09,
title = "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",
abstract = "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.",
keywords = "Bioanalysis, NUCLEOSIDE, SEMINAL PLASMA, REVERSE-TRANSCRIPTASE INHIBITORS, PHARMACOKINETICS, LC-MS/MS METHOD, HBV, ANTIRETROVIRAL DRUGS, HIV, HCV, Nucleoside reverse transcriptase inhibitor, Nucleotide reverse transcriptase inhibitor, SIMULTANEOUS QUANTIFICATION, HUMAN SERUM, CHRONIC HEPATITIS-C, STAVUDINE",
author = "Pereira, {Sofia de Azeredo Gaspar}",
year = "2013",
month = "1",
day = "1",
doi = "10.1016/j.jchromb.2013.01.005",
language = "Unknown",
volume = "919",
pages = "43--51",
journal = "Journal Of Chromatography B-Analytical Technologies In The Biomedical And L",
issn = "1570-0232",
publisher = "Elsevier Science B.V., Amsterdam.",
number = "NA",

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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

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 -