TY - JOUR
T1 - Simultaneous measurement of intracellular triphosphate metabolites of zidovudine, lamivudine and abacavir (carbovir) in human peripheral blood mononuclear cells by combined anion exchange solid phase extraction and LC-MS/MS
AU - Robbins, Brian L.
AU - Poston, Philip A.
AU - Neal, Erin F.
AU - Slaughter, Clive
AU - Rodman, John H.
N1 - Funding Information:
This work was supported in part by the American Lebanese Associated Charities, Pediatric AIDS Clinical Trials Group of the National Institutes of Allergy and Infectious Diseases and the Pediatric/Perinatal HIV Clinical Trials Network and Adolescent Trials Network of the National Institute of Child Health and Human Development and Glaxo SmithKline.
PY - 2007/5/1
Y1 - 2007/5/1
N2 - All nucleoside reverse transcriptase inhibitors (NRTI) must first be metabolized to their triphosphate forms in order to be active against HIV. Zidovudine (ZDV), abacavir (ABC) and lamivudine (3TC) have proven to be an efficacious combination. In order simultaneously to measure intracellular levels of the triphosphates (-TP) of ZDV, ABC (carbovir, CBV) and 3TC, either together or individually, we have developed a cartridge-LC-MS/MS method. The quantitation range was 2.5-250 pg/μl for 3TC-TP, 0.1-10.0 pg/μl for ZDV-TP and 0.05-5.00 pg/μl for CBV-TP. This corresponds to 0.1-11.0 pmol 3TC-TP per million cells, 4-375 fmol ZDV-TP per million cells and 2-200 fmol CBV-TP per million cells, extracted from 10 million cells. Patient samples demonstrated measured levels in the middle regions of our standard curves both at pre-dose and 4 h post-dose times.
AB - All nucleoside reverse transcriptase inhibitors (NRTI) must first be metabolized to their triphosphate forms in order to be active against HIV. Zidovudine (ZDV), abacavir (ABC) and lamivudine (3TC) have proven to be an efficacious combination. In order simultaneously to measure intracellular levels of the triphosphates (-TP) of ZDV, ABC (carbovir, CBV) and 3TC, either together or individually, we have developed a cartridge-LC-MS/MS method. The quantitation range was 2.5-250 pg/μl for 3TC-TP, 0.1-10.0 pg/μl for ZDV-TP and 0.05-5.00 pg/μl for CBV-TP. This corresponds to 0.1-11.0 pmol 3TC-TP per million cells, 4-375 fmol ZDV-TP per million cells and 2-200 fmol CBV-TP per million cells, extracted from 10 million cells. Patient samples demonstrated measured levels in the middle regions of our standard curves both at pre-dose and 4 h post-dose times.
KW - Antiviral drug metabolism
KW - Carbovir triphosphate
KW - Human immunodeficiency virus
KW - Lamivudine triphosphate
KW - Zidovudine triphosphate
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U2 - 10.1016/j.jchromb.2006.12.015
DO - 10.1016/j.jchromb.2006.12.015
M3 - Article
C2 - 17197254
AN - SCOPUS:34247253856
SN - 1570-0232
VL - 850
SP - 310
EP - 317
JO - Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences
JF - Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences
IS - 1-2
ER -
