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Randomized Controlled Trial
. 2008 Oct;30(5):611-9.
doi: 10.1097/FTD.0b013e318186e08e.

Studies 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

Naser L Rezk  1 , Nicole White, Arlene S Bridges, Mohamed F Abdel-Megeed, Tarek M Mohamed, Said S Moselhy, Angela D M Kashuba
Affiliations
Randomized Controlled Trial

Studies 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

Naser L Rezk et al. Ther Drug Monit. 2008 Oct.

Abstract

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.

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Figures

FIGURE 1
FIGURE 1
Chromatogram of low QC (80 ng/mL) in negative mode. The figure illustrates peaks for ZDV (266.0/223.0), d4T (22.9/42.0), and CMI (250.3/156.9) ion pair.
FIGURE 2
FIGURE 2
A, Chromatogram of low QC (80 ng/mL) in positive-mode first period. The figure illustrates peaks for ZDV (268.3/127.1), CMI (253.1/159.3), and 3TC (230.13/112.2) ion pair. B, Chromatogram of low QC (80 ng/mL) in positive-mode second period. The figure illustrates peaks for RTV (721.0/268.0), LPV (629.4/447.3), NFV (568.3/467.2), and NVP (267.1/226.1) ion pair.
FIGURE 2
FIGURE 2
A, Chromatogram of low QC (80 ng/mL) in positive-mode first period. The figure illustrates peaks for ZDV (268.3/127.1), CMI (253.1/159.3), and 3TC (230.13/112.2) ion pair. B, Chromatogram of low QC (80 ng/mL) in positive-mode second period. The figure illustrates peaks for RTV (721.0/268.0), LPV (629.4/447.3), NFV (568.3/467.2), and NVP (267.1/226.1) ion pair.
FIGURE 3
FIGURE 3
Percent deviation between 2 LC-MS/MS runs for 15 clinical samples.
FIGURE 4
FIGURE 4
Comparison of results between LC-MS/MS and LC-diode array detection (UV).
FIGURE 5
FIGURE 5
Chromatogram in negative mode for 1 clinical sample. The figure illustrates peaks for d4T (222.9/42.0) and IS CMI (250.3/156.9) ion pairs.
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References

    1. Connor EM, Sperling RS, Gelber R, et al. Reducing the risk of maternalinfant transmission of HIV: a door is opened. N Engl J Med. 1994;331:1173. - PubMed
    1. The Breastfeeding and HIV International Transmission Study Group. Coutsoudis A, Dabis F, et al. Late postnatal transmission of HIV-1 in breast-fed children: an individual patient data meta-analysis. J Infect Dis. 2004;189:2154. - PubMed
    1. De Cock KM, Fowler MG, Mercier E, et al. Prevention of mother-to-child HIV transmission in resource-poor countries: translating research into policy and practice. JAMA. 2000;283:1175. - PubMed
    1. Thior I, Shahin L, Smeaton L, et al. Breastfeeding plus infant zidovudine prophylaxis for 6 months vs formula feeding plus infant zidovudine for 1 month to reduce mother-to-child HIV transmission in Botswana: a randomized trial: the Mashi Study. JAMA. 2006;296:794. - PubMed
    1. UNAIDS. AIDSEpidemic Update—December 2003. Vol. 3. Geneva, Switzerland: Joint United Nation Program on HIV/AIDS; 2003. pp. 7–13.

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