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Antimicrobial Agents and Chemotherapy, November 2000, p. 3097-3100, Vol. 44, No. 11
Department of
Biochemistry1 and Department of
Medicine,3 School of Medicine, Medical Sciences
Campus, University of Puerto Rico, and Puerto Rico Health
Department (CLETS),4 San Juan, and
Department of Chemistry, Rio Piedras Campus, University of
Puerto Rico, Rio Piedras,2 Puerto Rico
Received 11 February 2000/Returned for modification 28 May
2000/Accepted 21 August 2000
Highly active antiretroviral therapy (HAART) is the standard
treatment for infection with human immunodeficiency virus (HIV). The
most common HAART regimen consists of the combination of at least one
protease inhibitor (PI) with two nucleoside reverse transcriptase
inhibitors (NRTIs). Contrary to PIs, NRTIs require intracellular
activation from the parent compound of their triphosphate moiety to
suppress HIV replication. Simultaneous intracellular determination of
two NRTI triphosphates is difficult to accomplish due to their
relatively small concentrations in peripheral blood mononuclear cells
(PBMCs), requiring large amounts of blood from HIV-positive patients.
Recently, we described a method to determine intracellular zidovudine
triphosphate (ZDV-TP) concentrations in HIV-infected patients by using
solid-phase extraction and tandem mass spectrometry. The limit of
quantitation (LOQ) for ZDV-TP was 0.10 pmol, and the method was
successfully used for the determination of ZDV-TP in HIV-positive
patients. In this study, we enhanced the aforementioned method by the
simultaneous quantitation of ZDV-TP and lamivudine triphosphate
(3TC-TP) in PBMCs from HIV-infected patients. The LOQ for 3TC-TP was
4.0 pmol, with an interassay coefficient of variation and an accuracy
of 7 and 12%, respectively. This method was successfully applied to
the simultaneous in vivo determination of the ZDV-TP and 3TC-TP
pharmacokinetic profiles from HIV-infected patients receiving HAART.
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Simultaneous Quantitation of Intracellular
Zidovudine and Lamivudine Triphosphates in Human Immunodeficiency
Virus-Infected Individuals
*
Corresponding author. Mailing address: Department of
Biochemistry, P.O. Box 365067, School of Medicine, Medical Sciences
Campus, University of Puerto Rico, San Juan Puerto Rico 00936-5067. Phone and Fax: (787) 754-4929. E-mail:
j_rodriguez{at}rcmaxp.upr.clu.edu.
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