Assay of the Acetyl-CoA Probe Acetyl-Sulfamethoxazole and of Sulfamethoxazole by Gas Chromatography-Mass Spectrometry

✍ Scribed by Z. Ying; K.C. Agarwal; M. Beylot; M.V. Soloviev; F. David; M. Reider; K.Y. Tserng; H. Brunengraber

• Publisher: Elsevier Science
• Year: 1993
• Tongue: English
• Weight: 441 KB
• Volume: 212
• Category: Article
• ISSN: 0003-2697
• DOI: 10.1006/abio.1993.1357

✦ Synopsis

We present gas chromatographic-mass spectrometric assays for (i) the concentration of sulfamethoxazole and (ii) the concentration and molar percentage enrichment of acetyl-sulfamethoxazole in biological fluids. The compounds are extracted with ethyl acetate, derivatized with either diazomethane or pentafluorobenzyl bromide, and analyzed by gas chromatography-mass spectrometry. Quantitation is achieved using internal standards, (\left[{ }^{2} \mathrm{H}{4}\right]) sulfamethoxazole and acetyl (\left[{ }^{2} \mathrm{H}{4}\right]) sulfamethoxazole. Limits of detection are (200 \mathrm{nmol}) for the methyl derivatives and (2 \mathrm{nmol}) for the pentafluorobenzyl derivatives. The high sensitivity of the assay with the pentafluorobenzyl derivatives allows measuring in plasma and urine (i) the pharmacokinetics of sulfamethoxazole and acetyl-sulfamethoxazole and (ii) the stable isotope enrichment of the acetyl moiety of acetylsulfamethoxazole. The latter is used as a probe for the noninvasive chemical biopsy of liver extramitochondrial acetyl-CoA. c 1993 Academic Press, Inc.