Abstract

A rapid and rugged solid-phase extraction-liquid chromatographic-electrospray tandem mass spectrometric method has been developed to quantitate two novel human leukocyte elastase inhibitors, SYN-1390 and SYN-1396, in rat plasma. A reversed-phase column and an isocratic mobile phase consisting of acetonitrile-water-formic acid (70:30:0.2, v/v/v) were used. The mass spectrometer was operated in the multiple reaction monitoring mode. For both analytes, standard curves were linear over a working range of 0.1–20 μg ml−1 (r≥0.995) and the limit of quantitation was 0.1 μg ml−1 with a 150 μl plasma volume. This assay proved to be useful for the determination of SYN-1390 and SYN-1396 in plasma samples from pharmacokinetic study.

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