Analysis of naltrexone and 6-beta-naltrexol in plasma and urine by gas chromatography/negative ion chemical ionization mass spectrometry.

A procedure for the analysis of naltrexone and 6-beta-naltrexol in plasma and urine samples is described. The method takes advantage of the specificity of negative ion chemical ionization mass spectrometry and the resolving power of capillary column chromatography to achieve a limit of quantitation of 0.1 ng/mL. The trideuterated analogs of naltrexone and 6-beta-naltrexol are used as internal standards. Samples are first made basic with K2HPO4 buffer (50% w/v), and then extracted twice with n-butyl chloride-acetonitrile (4:1). After back extraction into 0.2 N H2SO4, the samples are again extracted with n-butyl chloride-acetonitrile. The extracts are derivatized with 2% methoxyamine in pyridine and pentafluoropropionic anhydride to form the methoxime bis-(pentafluoropropionyl) derivative of naltrexone and the tris-(pentafluoropropionyl) derivative of 6-beta-naltrexol. The derivatized extracts are analyzed by selected ion monitoring of prominent ions formed by electron-capture negative ion chemical ionization.