Liquid chromatography-mass spectrometry assay of a thiadiazole derivative in mice: Application to pharmacokinetic studies

Hong Wong, Lee Jia, Jim B. Camden, Steve D. Weitman

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Modern atmospheric pressure ionization (API) ion-trap mass spectrometry in connection with fast chromatographic separations using a short narrow-bore C8 column was developed to determine 5-phenyl-3-thioureido-1,2,4-thiadiazole (301029), a novel virus inhibitor in serum. Both 301029 and an internal standard (I.S.) were separated from serum samples by acetonitrile deproteinization and extraction without time-consuming reconstitution. The chromatographic separation was achieved on a C8 reversed-phase narrow-bore column using acetonitrile-water-acetic acid (90:10:0.01, v/v/v) as a mobile phase. The mass spectrometric analysis was performed by atmospheric pressure chemical ionization (APCI) mode with positive ion detection. Single ion monitoring (SIM) scan mode of m/z 237 and 158 was used to quantitatively determine 301029 and I.S., respectively. The low limit of quantitation was 25 ng/ml. The assay exhibited a linear range of 25-2500 ng/ml. Recovery from serum proved to be 100-113%. The precision (C.V.) and accuracy (RE) of the method were 2-12% and 94-112%, respectively. The present method was applied to determine the pharmacokinetic parameters of 301029 following oral administration of the agent to mice at 5 g/kg. The results revealed that the elimination half-life of 301029 was 413 min and the area under serum concentration-time curve was 354 μg/ml/min.

Original languageEnglish (US)
Pages (from-to)55-62
Number of pages8
JournalJournal of Chromatography B: Biomedical Sciences and Applications
Volume765
Issue number1
DOIs
StatePublished - Dec 5 2001

Keywords

  • 5-Phenyl-3-thioureido-1,2,4-thiadiazole
  • Thiadiazoles

ASJC Scopus subject areas

  • Chemistry(all)

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