Time filter

Source Type

Jiang H.,Bioanalytical science Analytical and Bioanalytical science | Zeng J.,Bioanalytical science Analytical and Bioanalytical science | Li W.,Biotransformation Pharmaceutical Candidate Optimization | Bifano M.,Bristol Myers Squibb | And 7 more authors.
Analytical Chemistry | Year: 2012

A strategy of using selected reaction monitoring (SRM) mass spectrometry for evaluating oral absolute bioavailability with concurrent intravenous (IV) microdosing a stable isotopically labeled (SIL) drug was developed and validated. First, the isotopic contribution to SRM (ICSRM) of the proposed SIL drug and SIL internal standard (IS) was theoretically calculated to guide their chemical synthesis. Second, the lack of an isotope effect on drug exposure was evaluated in a monkey study by IV dosing a mixture of the SIL and the unlabeled drugs. Third, after the SIL drug (100 μg) was concurrently IV dosed to humans, at Tmax of an oral therapeutic dose of the unlabeled drug, both drugs in plasma specimens were simultaneously quantified by a sensitive and accurate SRM assay. This strategy significantly improves bioanalytical data quality and saves time, costs, and resources by avoiding a traditional absolute bioavailability study or the newer approach of microdoses of a radio-microtracer measured by accelerator mass spectrometry. © 2012 American Chemical Society. Source

Discover hidden collaborations