title: MALDI-TOF mass spectrometric determination of eight benzodiazepines with two of their metabolites in blood.
abstract: 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, α-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-d5 as the internal standard. The limit of detection of zolpidem was 0.07ng/ml with its quantification range of 0.2-20ng/ml in blood, in the best case, and the limit of detection of flunitrazepam was 2ng/ml with its quantification range of 6-200ng/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 20μl of blood. The developed method was successfully used for the determination of BZDs in biological fluids obtained from two victims.
authors.affiliation: Department of Legal Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192, Japan. Electronic address: hnozawa@hama-med.ac.jp.
authors.forename: Hideki
authors.initials: H
authors.lastname: Nozawa
authors.affiliation: Department of Legal Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192, Japan.
authors.forename: Kayoko
authors.initials: K
authors.lastname: Minakata
authors.affiliation: Department of Legal Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192, Japan.
authors.forename: Itaru
authors.initials: I
authors.lastname: Yamagishi
authors.affiliation: Department of Legal Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192, Japan.
authors.forename: Koutaro
authors.initials: K
authors.lastname: Hasegawa
authors.affiliation: Department of Legal Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192, Japan.
authors.forename: Amin
authors.initials: A
authors.lastname: Wurita
authors.affiliation: Department of Legal Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192, Japan.
authors.forename: Kunio
authors.initials: K
authors.lastname: Gonmori
authors.affiliation: Department of Legal Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Suzuki
authors.affiliation: Department of Legal Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192, Japan.
authors.forename: Kanako
authors.initials: K
authors.lastname: Watanabe
mesh_terms: D053961:Azabicyclo Compounds / Q000097:blood; D001569:Benzodiazepines / Q000097:blood* / Q000378:metabolism; D005445:Flunitrazepam / Q000097:blood; D006801:Humans; D010879:Piperazines / Q000097:blood; D011725:Pyridines / Q000097:blood; D021241:Spectrometry, Mass, Electrospray Ionization; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*; D053719:Tandem Mass Spectrometry; D000077334:Zolpidem
chemical_list: D053961:Azabicyclo Compounds; D010879:Piperazines; D011725:Pyridines; C515050:zopiclone; D001569:Benzodiazepines; D005445:Flunitrazepam; D000077334:Zolpidem
keywords: Benzodiazepines; Blood; MALDI-TOF mass spectrometry; α-Cyano-4-hydroxy cinnamic acid