{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T11:49:14Z","timestamp":1778586554141,"version":"3.51.4"},"reference-count":21,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2015,5,5]],"date-time":"2015-05-05T00:00:00Z","timestamp":1430784000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Mass Spectrom."],"published-print":{"date-parts":[[2015,6]]},"abstract":"<jats:p>Although zidovudine (AZT) is not the preferred antiretroviral drug for adult HIV\u2010infected patients, it is still widely used in infants for both prevention of mother\u2010to\u2010infant HIV\u20101 transmission and treatment of HIV\u2010infected children. However, it is difficult to measure intracellular concentrations of AZT metabolites in small blood samples due to their extremely low concentrations in peripheral blood mononuclear cells and interference by endogenous nucleotide triphosphates, residual plasma phosphates and electrolytes. We developed an ultrasensitive assay using liquid chromatography\u2013tandem mass spectrometry (LC\u2013MS\/MS) for measurement of intracellular concentrations of zidovudine (AZT)\u2010monophosphate (AZT\u2010MP), \u2010diphosphate (AZT\u2010DP) and \u2010triphosphate (AZT\u2010TP). The high sensitivity was due to the improvement of peripheral blood mononuclear cells extraction for complete removal of plasma and electrolytes, alkalization of LC buffer and use of alkaline\u2010stable high performance liquid chromatography column and tetrabutylammonium hydroxide as the ion pair. Using this method, the lower limits of quantification of AZT, AZT\u2010MP, \u2010DP and \u2010TP were 6, 6, 10 and 10\u2009fmol per sample, respectively. Accuracy ranged 89\u2013115% and precision was lower than 15% in the quantification range of 6\u20136000\u2009fmol\/sample for plasma AZT and intracellular AZT\u2010MP and 10\u201310\u2009000\u2009fmol\/sample for AZT\u2010DP and \u2010TP. The validation parameters met the international requirements. Among nine AZT\u2010treated HIV\u2010infected adult patients, five had low AZT\u2010TP levels (&lt;10\u2009fmol\/10<jats:sup>6<\/jats:sup> cells). Our assay has high sensitivity and is advantageous for evaluation of AZT phosphates in children and infants based on minimum blood sampling requirement. Copyright \u00a9 2015 John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/jms.3577","type":"journal-article","created":{"date-parts":[[2015,5,12]],"date-time":"2015-05-12T06:05:44Z","timestamp":1431410744000},"page":"783-791","source":"Crossref","is-referenced-by-count":6,"title":["Ultrasensitive method to quantify intracellular zidovudine mono\u2010, di\u2010 and triphosphate concentrations in peripheral blood mononuclear cells by liquid chromatography\u2013tandem mass spectrometry"],"prefix":"10.1002","volume":"50","author":[{"given":"Ei","family":"Kinai","sequence":"first","affiliation":[{"name":"AIDS Clinical Center National Center for Global Health and Medicine  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroyuki","family":"Gatanaga","sequence":"additional","affiliation":[{"name":"AIDS Clinical Center National Center for Global Health and Medicine  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshimi","family":"Kikuchi","sequence":"additional","affiliation":[{"name":"AIDS Clinical Center National Center for Global Health and Medicine  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shinichi","family":"Oka","sequence":"additional","affiliation":[{"name":"AIDS Clinical Center National Center for Global Health and Medicine  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shingo","family":"Kato","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, School of Medicine Keio University  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,5,5]]},"reference":[{"key":"e_1_2_5_2_1","unstructured":"United States Department of Health and Human Services.Panel on antiretroviral guidelines for adults and adolescents \u2013 a working group of the Office of AIDS Research Advisory Council (OARAC). Guidelines for the use of antiretroviral agents in HIV\u20101\u2010infected adults and adolescents. November 13 2014. Available athttp:\/\/aidsinfo.nih.gov\/guidelines"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(99)07219-0"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/00002030-200308150-00006"},{"key":"e_1_2_5_5_1","doi-asserted-by":"crossref","first-page":"2555","DOI":"10.1128\/AAC.01130-07","article-title":"High levels of zidovudine (AZT) and its intracellular phosphate metabolites in AZT\u2010 and AZT\u2010lamivudine\u2010treated newborns of human immunodeficiency virus\u2010infected mothers","volume":"62","author":"Durand\u2010Gasselin L.","year":"2008","journal-title":"Antimicrob. 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