Capillary gas chromatographic-mass spectrometric analysis of 15-deoxy-16-hydroxy-16-vinylprostaglandin E2

A new topically active antihypertensive agent, the methyl ester of 15-deoxy-16-hydroxy-16-vinylprostaglandin E2 (1), rapidly hydrolyzes in blood to the carboxylic acid 2, which also has antihypertensive activity. A capillary gas chromatographic-mass spectrometric method is described for measuring 2 in human plasma or serum at expected experimental blood levels of 75-1500 pg/mL. The assay is based on selected-ion monitoring of the carboxylate anion formed from negative ion chemical ionization of the trimethylsilylpentafluorobenzyl ester of 2, using a trideuterated analogue of 2 as internal standard. The method has been used to analyze samples from subjects following topical application of 1-2 mg of 1. Sample preparation included isolation from 1 mL of plasma or serum and purification of the ester derivative with C18 cartridges, followed by a two-step trimethylsilylation.