Open AccessStudies on Antiretroviral Drug Concentrations in Breast Milk: Validation of a Liquid Chromatography-Tandem Mass Spectrometric Method for the Determination of 7 Anti-Human Immunodeficiency Virus Medications
Author(s) -
Naser L. Rezk,
Nicole White,
Arlene S. Bridges,
Mohamed F. AbdelMegeed,
Tarek M. Mohamed,
Said S Moselhy,
Angela D. M. Kashuba
Publication year - 2008
Publication title -
therapeutic drug monitoring
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.649
H-Index - 93
eISSN - 1536-3694
pISSN - 0163-4356
DOI - 10.1097/ftd.0b013e318186e08e
Subject(s) - nevirapine , zidovudine , lamivudine , stavudine , ritonavir , breast milk , nelfinavir , lopinavir , efavirenz , pharmacokinetics , chromatography , analyte , drug , therapeutic drug monitoring , pharmacology , chemistry , medicine , virology , virus , viral load , antiretroviral therapy , viral disease , hepatitis b virus , biochemistry
Studying the pharmacokinetics of antiretroviral drugs in breast milk has important implications for the health of both the mother and the infant, particularly in resource-poor countries. Breast milk is a highly complex biological matrix, yet it is necessary to develop and validate methods in this matrix, which simultaneously measure multiple analytes, as women may be taking any number of drug combinations to combat human immunodeficiency virus infection. Here, we report a novel extraction method coupled to high-performance liquid chromatography and tandem mass spectrometry for the accurate, precise, and specific measurement of 7 antiretroviral drugs currently prescribed to infected mothers. Using 200 microL of human breast milk, simultaneous quantification of lamivudine (3TC), stavudine (d4T), zidovudine (ZDV), nevirapine (NVP), nelfinavir (NFV), ritonavir, and lopinavir was validated over the range of 10-10,000 ng/mL. Intraday accuracy and precision for all analytes were 99.3% and 5.0 %, respectively. Interday accuracy and precision were 99.4 % and 7.8%, respectively. Cross-assay validation with UV detection was performed using clinical breast milk samples, and the results of the 2 assays were in good agreement (P = 0.0001, r = 0.97). Breast milk to plasma concentration ratios for the different antiretroviral drugs were determined as follows: 3TC = 2.96, d4T = 1.73, ZDV = 1.17, NVP = 0.82, and NFV = 0.21.