A fast LC-APCI/MS method for analyzing benzodiazepines in whole blood using monolithic support

A simple and fast procedure was developed for the simultaneous determination of eight benzodiazepines (BZDs) in whole blood using liquid chromatography-atmospheric pressure chemical ionization-mass spectrometry (LC-APCI-MS). Sample pretreatment was carried out using a simple liquid–liquid extraction (LLE) with n-butylchloride, and chromatographic separation was performed using a monolithic silica column to speed up the analytical process. APCI and electrospray ionization (ESI) were compared. Whereas both ionization techniques appeared suitable for BZDs, APCI was found to be slightly more sensitive, especially for the determination of frequently low-dosed compounds. The method was validated according to the guidelines of the “Société Française des Sciences et Techniques Pharmaceutiques” (SFSTP) in the concentration range of 2.5–500 μg/L. The limit of quantification (LOQ) was 2.5 μg/L for all the compounds. Validation data including linearity, precision, and trueness were obtained, allowing subtherapeutic quantification of frequently low-dosed BZDs. The high selectivity of the mass spectrometer, along with the properties of the monolithic support, allowed unequivocal analysis of the eight compounds in less than 5 min. To demonstrate the potential of the method, it was used for the analysis of benzodiazepines in postmortem blood samples.