Journal of Analytical Toxicology

Transcription

1 Journal of Analytical Toxicology jat.oxfordjournals.org 203 Media Kit Advertising & Sales Contacts Allan Kolstein Corporate Account Manager e: For reprints, eprints or tailored products: e: ISSN (Print) ISSN (Online) JOURNAL OF Analytical Volume 36, Number 6: Pages Toxicology JULY/AUGUST 202 Worldwide readership includes toxicologists, pathologists, chemists, clinicians, researchers, and educators working in medical, university, law enforcement, and industry laboratories. The Journal of Analytical Toxicology (JAT) is a peer-reviewed international publication devoted to the timely dissemination of scientific communications concerning the isolation, identification, and quantification of drugs and other potentially toxic substances. Official journal of the Society of Forensic Toxicologists (SOFT) J A T Useful Information Print Circulation:,750 Geographic Breakdown: North America 5% - Europe 27% - UK 7% - Japan 3% - Rest of World 2% Average Monthly Page Views: 43,000 Average Available Ad Impressions: 87,05* *Combined monthly leaderboard and skyscraper positions Impact Factor: Target Audience: Toxicologists, Pathologists, Chemists Frequency: 9 Peer Reviewed: Yes Editor-In-Chief: Bruce A. Goldberger, Ph.D., DABFT

2 203 Schedule Volume Issue Cover Month Ad artwork due Mailout Date Bonus Conference Distribution 37/ Jan/Feb 24 December January /2 March 23 January February /3 April 26 February March /4 May 2 March April /5 June 29 April May /6 Jul/Aug 4 June July /7 September 9 July August /8 October 22 August September /9 Nov/Dec 27 September October 203 Society of Forensic Toxicologists 27 October November 203 Orlando

3 ISSN (Print) ISSN (Online) ISSN (Print) ISSN (Online) Journal of Analytical Toxicology 202;36: doi:0.093/jat/bks059 Advance Access publication July 23, 202 Article Stephanie J. Marin *, Mark Roberts 2, Michelle Wood 2 and Gwendolyn A. McMillin 3,4 ARUP Institute for Clinical and Experimental Pathology, Salt Lake City, Utah, 2 Waters Corporation, MS Technologies Centre, Manchester, UK, 3 ARUP Laboratories, Inc., Salt Lake City, UT, and 4 Department of Pathology, University of Utah School of Medicine, Salt Lake City, Utah *Author to whom correspondence should be addressed. stephanie.marin@aruplab.com This paper reports an ultra-performance liquid chromatography tandem mass spectrometry (UPLC MS-MS) method to quantitate 2 benzodiazepines, zolpidem and zopiclone in serum and plasma. After liquid liquid extraction, an Acquity UPLC with a TQ Detector and BEH C8 column was used (Waters, Milford, MA). The injection-to-injection run time was 7.5 min. Forty-eight authentic serum and plasma patient specimens were analyzed and results compared to those obtained using a previously published method. Average r 2 values for linearity ( to,000 ng/ml over five days) were all above 0.995, except a-hydroxytriazolam (0.993). Intra-day and inter-day relative standard deviation values were within +5% and the percent deviation from the expected concentrations were within +%. Recovery ranged from 62 to 89%. Matrix effects ranged from 28% to 6%. The limits of detection were ng/ml, except for lorazepam, nordiazepam, oxazepam and temazepam (5 ng/ml). Ion ratios were +5% for all analytes. For authentic patient specimens (n 5 48, 76 positive results), there was excellent correlation between the UPLC MS-MS results and the previous method. The best least-squares fit had an equation of y x.652, r This UPLC MS-MS method is suitable for the quantification of benzodiazepines and hypnotics in serum and plasma, and offers fast, reliable and sensitive results. Although numerous analytical methods for quantitation of benzodiazepines have been reported previously (5 3), here we present a quantitative ultra-performance liquid chromatography tandem mass spectrometry (UPLC MS-MS) method for serum or plasma, unique because it identifies the hypnotics zolpidem and zopiclone, as well as 2 benzodiazepines and metabolites: 7-aminoclonazepam, 7-aminoflunitrazepam, a-hydroxyalprazolam, a-hydroxymidazolam, a-hydroxytriazolam, alprazolam, bromazepam, chlordiazepoxide, diazepam, estazolam, flunitrazepam, lormetazepam, lorazepam, midazolam, nordiazepam, nitrazepam, oxazepam, prazepam, temazepam, triazolam and clonazepam. As part of the validation, 48 patient specimens (76 positive results) were compared to a previously validated high-performance liquid chromatography (HPLC) MS-MS method (5). Experimental Reagents and standards Certified reference material for the benzodiazepines and metabolites (7-aminoclonazepam, 7-aminoflunitrazepam, a-hydroxyalprazolam, a-hydroxymidazolam, a-hydroxytriazolam, alprazolam, bromazepam, chlordiazepoxide, diazepam, estazolam, flunitrazepam, lormetazepam, lorazepam, midazolam, nordiazepam, nitrazepam, oxazepam, prazepam, temazepam, triazolam and clona- Introduction zepam) and zolpidem and zopiclone were purchased as methanolic Benzodiazepines are a schedule IV class of drugs in the United solutions ( mg/ml) from LGC Standards (Teddington, UK). Mixed States, prescribed for their sedative, anxiolytic and anticonvulsant properties. They are some of the most frequently presequent dilution with water. working solutions for the benzodiazepines were prepared by subscribed drugs in the Western world. Of the top 200 drugs Deuterated analogues were also obtained from the same supplier as 0. mg/ml solutions in methanol: 7-aminoclonazepam-d4, prescribed in the US by number of prescriptions, six were benzodiazepines (alprazolam ranked number 9, clonazepam 26, 7-aminoflunitrazepam-d7, a-hydroxyalprazolam-d5, a-hydroxytriazolam-d5, alprazolam-d5, clonazepam-d4, diazepam-d5, lorazepam 28, diazepam 45, and temazepam 63) (). Zolpidem, a non-benzodiazepine sleep aid, was ranked number 6. estazolam-d5, flunitrazepam-d7, nordiazepam-d5, nitrazepam-d5, Benzodiazepines are used to manage anxiety, insomnia, agitation, muscle spasms and alcohol withdrawal. Many benzodiaze- reference material stocks were stored at 208C until use. oxazepam-d5, prazepam-d5, triazolam-d4 and zolpidem-d6. All pines are potentially addictive and may be abused. They are The solvents used for mobile phases were LC MS grade and often used recreationally in combination with other drugs, particularly cocaine and heroin. They are commonly reported in rate decahydrate, dichloromethane, hexane, ether and isoamyl purchased from Sigma Aldrich (Poole, UK). Disodium tetrabo- poisonings and suicides, and are used for drug-facilitated crime alcohol used in the extraction procedure were also from Sigma due to their sedative properties and amnesic effects. Effects may Aldrich. be exacerbated when combined with other central nervous system (CNS) depressants such as alcohol (2). There are case reports of amnesia, nocturnal eating, sleep-walking and sleepdriving after taking zolpidem (3). Therefore, it is important to quality control samples Deuterated internal standard solution, calibrators and accurately identify and quantitate these drugs to document an A mixed working internal standard (IS) solution was prepared exposure, characterize a possible overdose, and to support daily by dilution of the deuterated analogues into mobile phase therapeutic drug monitoring and dose optimization (4). A at a concentration of 5 mg/ml. The blank serum, used for # The Author [202]. Published by Oxford University Press. All rights reserved. For Permissions, please journals.permissions@oup.com Print Advertising Options & Rates Display Rates insertion Special Position Premiums $560 $530 $485 $470 $385 $355 $30 $295 ½ Page $450 $435 $395 $380 ½ Page $275 $260 $220 $205 ¼ Page $360 $345 $35 $305 ¼ Page $85 $70 $40 $30 Cover 4-50% extra Cover 3-40% extra Cover 2-0% extra Facing Leading Article 0% extra Facing Contents 0% extra Incentives Agency Commission 5% Double Page Spread = 2 x Full page rate More options and solutions in partnership with Journal of Analytical Toxicology Loose and Bound Inserts available JOURNAL OF Volume 36, Number 6: Pages JULY/AUGUST 202 Analytical Toxicology JOURNAL OF Volume 36, Number 6: Pages JULY/AUGUST 202 Analytical Toxicology Sensitive UPLC MS-MS Assay for 2 Benzodiazepine Drugs and Metabolites, Zolpidem and Zopiclone in Serum or Plasma J A T J A T Belly Band Sponsored supplements published and distributed with the journal Article reprints and eprints useful as conference handouts

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