A rapid and reliable solid-phase extraction-LC/MS/MS assay for the determination of two novel human leukocyte elastase inhibitors, SYN-1390 and SYN-1396, in rat plasma

A rapid and rugged solid-phase extraction-liquid chromatographic-electrospr ay tandem mass spectrometric method has been developed to quantitate tale n ovel human leukocyte elastase inhibitors, SYN-1390 and SYN-1396, in rat pla sma. A reversed-phase column and an isocratic mobile phase consisting of ac etonitrile-water-formic acid (70:30:0.2, v/v/v) were used. The mass spectro meter was operated in the multiple reaction monitoring mode. For both analy tes, standard curves were linear over a working range of 0.1-20 mu g ml(-1) (r greater than or equal to 0.995) and the limit of quantitation was 0.1 m u g ml(-1) with a 150 mu l plasma volume. This assay proved to be useful fo r the determination of SYN-1390 and SYN-1396 in plasma samples from pharmac okinetic study. (C) 1999 Elsevier Science B.V. All rights reserved.