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Simultaneous analysis of diphenhydramine and a stable isotope analog ( 2 H 10 )diphenhydramine using capillary gas chromatography with mass selective detection in biological fluids from chronically instrumented pregnant ewest
Author(s) -
Tonn G. R.,
Mutlib A.,
Abbott F. S.,
Rurak D. W.,
Axelson J. E.
Publication year - 1993
Publication title -
biological mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 121
eISSN - 1096-9888
pISSN - 1052-9306
DOI - 10.1002/bms.1200221103
Subject(s) - chromatography , amniotic fluid , chemistry , diphenhydramine , mass spectrometry , capillary action , gas chromatography , fetus , pharmacology , medicine , histamine , materials science , pregnancy , genetics , composite material , biology
This report describes both the synthesis of a stable isotope analog of the H 1 receptor antagonist diphenhydramine (DPHM), and the simultaneous quantitation of DPHM and a deuterated stable isotope analog of DPHM, viz. ( 2 H 10 )DPHM in biological fluids from the chronically instrumented pregnant ewe. ( 2 H 10 )DPHM was synthesized and purified, and both its structure and purity were verified. Biological samples were prepared for analysis using liquid‐liquid extraction prior to capillary gas chromatography/mass spectrometry. The method employed electron impact ionization with selective ion monitoring of ions with m/z 165 for DPHM and m/z 173 for ( 2 H 10 )DPHM. The minimal quantifiable concentration of DPHM and ( 2 H 10 )DPHM from a 1.0 ml sample was 2.0 ng ml −1 in fetal and maternal plasma, fetal tracheal fluid and amniotic fluid. The method was validated from 2.0 ng ml −1 to 200.0 ng ml −1 for both DPHM and ( 2 H 10 )DPHM in plasma, fetal tracheal fluid and amniotic fluid. Differences in the disposition between DPHM and ( 2 H 10 )DPHM were not apparent during a control experiment in which both labeled and unlabeled DPHM were administered to a chronically instrumented fetal lamb. This method provides the required sensitivity and selectivity for the simultaneous quantitation of unlabeled and labeled DPHM during pharmacokinetic experiments conducted in near‐term pregnant sheep.