Quantification of dideoxycytidine in human plasma by gas chromatography/mass spectrometry

A gas chromatographic/mass spectrometric procedure has been developed for the quantification in plasma of dideoxycytidine (DDC), a candidate anti-AIDS drug. The assay uses an extraction with ethyl acetate containing 10% methanol followed by three derivatization steps: (i) reaction with t-butyl dimet...

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Bibliographic Details
Published inBiomedical & environmental mass spectrometry Vol. 17; no. 5; p. 399
Main Authors Rubio, F R, Crews, T, Garland, W A, Fukuda, E K
Format Journal Article
LanguageEnglish
Published England 01.11.1988
Subjects
Acquired Immunodeficiency Syndrome - blood
Acquired Immunodeficiency Syndrome - drug therapy
Dideoxynucleosides - blood
Dideoxynucleosides - therapeutic use
Gas Chromatography-Mass Spectrometry
Humans
Zalcitabine
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Summary:A gas chromatographic/mass spectrometric procedure has been developed for the quantification in plasma of dideoxycytidine (DDC), a candidate anti-AIDS drug. The assay uses an extraction with ethyl acetate containing 10% methanol followed by three derivatization steps: (i) reaction with t-butyl dimethyl chlorosilane to silylate the 5'-hydroxyl group; (ii) pentafluorobenzoylation of the amino group with pentafluorobenzoyl chloride; (iii) methylation of the ring nitrogen adjacent to the amino group with diazomethane. The resulting derivative is quantified using stable isotope dilution, selective ion monitoring and methane negative chemical ionization mass spectrometry. Plasma concentrations of DDC were measured over a range of 2-200 ng ml-1 using 1 ml plasma for extraction.
ISSN:0887-6134
2376-3868
DOI:10.1002/bms.1200170509