Determination of Benzodiazepines in Oral Fluid Using LC-MS-MS

Abstract

[Abstract IA rapid, simple, highly sensitive procedure for the simultaneous analysis of bromazepam, alprazolam, clonazepam, Iorazepam, oxazepam, diazepam, midazolam, flurazepam, flunitrazepam, nordiazepam, triazolam, temazepam, nitrazepam, and chlordiazepoxide in oral fluid is described, using liquid chromatography coupled to a triple quadrupole mass spectrometer in positive electrospray mode. Benzodiazepines in oral fluid samples (1 mL) were analyzed using the Quantisal TM collection device, quantified using solid-phase extraction, and detected using liquid chromatography with tandem mass spectrometric detection. For confirmation, two transitions were monitored and one ion ratio determined, which was within 20% of the ratio for known calibration standards. The limits of quantitation ranged from 0.5-5 ng/mL of neat oral fluid; the intraday precision of the assays (n = 5) ranged from 2.8-7.29%; and the interday precision ranged from 1.42-6.8% (n = 5). The percentage recovery of the drugs from the collection pads ranged from a low of 81.4% for midazolam to the highest of 90.17% for nitrazepam. The procedure can be applied to authentic oral fluid specimens.

Development and validation of a liquid chromatography–atmospheric pressure photoionization–mass spectrometry method for the quantification of alprazolam, flunitrazepam, and their main metabolites in haemolysed blood

“…Since the lowest concentration levels for each compound were included in the acceptance limits, they were considered as the LLOQ (1, 13, 3 and 2 ng/mL for ALZ, HALZ, FLZ and AFLZ, respectively). In comparison with ESI and APCI, the LOQ achieved for ALZ and FLZ in APPI with our single quadrupole MS was analogous to those obtained in the literature in ESI with triple quadrupole MS or ion trap MS (in the 0.5-5.0 ng/mL range) [11,[62][63][64][65][66] and in APCI with single quadrupole MS or ion trap MS (in the 1.0-5.0 ng/mL range) [20,44,67,68].…”

2007 National Roadside Survey of Alcohol and Drug Use by Drivers: Drug Results

“…The most common benzodiazepine is diazepam (Valium®) and/or its metabolites: nordiazepam, oxazepam, and temazepam. The confirmation procedure for the 2007 study included LC/MS/MS confirmation using the method described in Moore, Coulter, Crompton, and Zumwalt (2007).…”

Simultaneous determination of benzodiazepines and their metabolites in human serum by liquid chromatography–tandem mass spectrometry using a high‐resolution octadecyl silica column compatible with aqueous compounds

“…ESI, as a very soft ionization technique, is the most suitable for labile metabolites, and is therefore preferred in metabolite analysis (Kostiainen et al, 2003). The analysis of benzodiazepines and their metabolites can be performed using ESI-LC-MS (Jourdil et al, 2003) and ESI-LC-tandem mass spectrometry (MS/MS) (Liu et al, 2001;Chèze et al, 2004;Kintz et al, 2005;Laloup et al, 2005;Villain et al, 2005;Hegstad et al, 2006;Miller 358 et al, 2006;Quintela et al, 2006;Feng et al, 2007;Laloup et al, 2007;Li et al, 2007;Moore et al, 2007) as well as APCI-LC-MS (Kratzsch et al, 2004;Bugey et al, 2006) and APCI-LC-MS/MS (Smink et al, 2004(Smink et al, , 2006Ngwa et al, 2007). A conventional reversed-phase C 18 column is popularly used in the abovementioned LC-MS/MS methods.…”