Abstract
Selection of a new drug discovery candidate from a series of compounds requires a means of performing rapid analytical method development and sensitive quantitation of each drug in serum, plasma or other biological matrices. Information on serum/plasma concentration, bioavailability and half-life can often aid the discovery process by selecting those candidates with the desired pharmacokinetic parameters. In one series of farnesyl protein transferase (FPT) inhibitors, gas chromatography with nitrogen–phosphorus detection (NPD) was initially used to analyze samples from pharmacokinetic studies in mice and monkeys. Typical turnaround times using this technique approached 2–4 weeks for method development, quantitation of study samples and calculation of pharmacokinetic parameters. Once LC–atmospheric pressure ionization (API) MS–MS analysis was implemented in these same studies, they could be completed in less than one week. The advantages of using LC–API-MS–MS to aid in the drug candidate selection process is demonstrated for one compound (SCH 44342) in this series of FPT inhibitors.
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