MALDI-TOF mass spectrometric determination of eight benzodiazepines with two of their metabolites in blood

A rapid and sensitive method was developed for the determination of benzodiazepines and benzodiazepine-like substances (BZDs) by matrix-assisted laser desorption ionization (MALDI)-time-of-flight (TOF)-mass spectrometry (MS). In this method, alpha-cyano-4-hydroxy cinnamic acid was used as the matrix to assist the ionization of BZDs. Determination of 8 BZDs (with two of their metabolites) belonging to top 12 medical drugs detected in poisonous cases in Japan, was performed using diazepam-d(5) as the internal standard. The limit of detection of zolpidem was 0.07 ng/ml with its quantification range of 0.2-20 ng/ml in blood, in the best case, and the limit of detection of flunitrazepam was 2 ng/ml with its quantification range of 6-200 ng/ml in blood, in the worst case. The spectra of zopiclone in MALDI-MS and MS/MS were different from those in electrospray ionization MS and MS/MS. Present method provides a simple and high throughput method for the screening of these BZDs using only 20 mu l of blood. The developed method was successfully used for the determination of BZDs in biological fluids obtained from two victims. (C) 2014 Elsevier Ireland Ltd. All rights reserved.