Metabolites of lorazepam: Relevance of past findings to present day use of LC-MS/MS in analytical toxicology.
Summary of "Metabolites of lorazepam: Relevance of past findings to present day use of LC-MS/MS in analytical toxicology."
The advent of liquid chromatography-tandem mass spectrometry (LC-MS/MS), with the sensitivity it confers, permits the analysis of both phase I and II drug metabolites that in the past would have been difficult to target using other techniques. These metabolites may have relevance to current analytical toxicology employing LC-MS/MS, and lorazepam was chosen as a model drug for investigation, as only the parent compound has been targeted for screening purposes. Following lorazepam administration (2 mg, p.o.) to 6 volunteers, metabolites were identified in urine by electrospray ionization LC-MS/MS, aided by the use of deuterated analogues generated by microsomal incubation for use as internal chromatographic and mass spectrometric markers. Metabolites present were lorazepam glucuronide, a quinazolinone, a quinazoline carboxylic acid, and two hydroxylorazepam isomers, one of which is novel, having the hydroxyl group located on the fused chlorobenzene ring. The quinazolinone, and particularly the quinazoline carboxylic acid metabolite, provided longer detection windows than lorazepam in urine extracts not subjected to enzymatic hydrolysis, a finding that is highly relevant to toxicology laboratories that omit hydrolysis in order to rapidly reduce the time spent on gas chromatography-mass spectrometry (GC-MS) analysis. With hydrolysis, the longest windows of detection were achieved by monitoring lorazepam, supporting the targeting of the aglycone with free drug for those incorporating hydrolysis in their analytical toxicology procedures. Copyright © 2011 John Wiley & Sons, Ltd.
Department of Forensic Science & Drug Monitoring, King's College London, 150 Stamford Street, London SE1 9NH, UK.
This article was published in the following journal.
Name: Drug testing and analysis
The objective of this study was to compare the performance of an immunoassay screening for synthetic cannabinoids with a newly developed confirmation method using liquid chromatography quadrupole time...
Diplopia - seeing double - is a symptom with many potential causes, both neurological and ophthalmological. Benzodiazepine induced ocular side-effects are rarely reported. Lorazepam is one of the comm...
Computational methods have been widely applied to toxicology across pharmaceutical, consumer product and environmental fields over the past decade. We have reviewed progress in computational toxicolog...
This study will compare the effects of an acute dose of lorazepam to a placebo in elderly patients with generalized anxiety disorder (GAD).
The purpose of this study is to evaluate intranasal lorazepam in paediatric status epilepticus. This is a potentially, more effective, safer and cheaper treatment for a common paediatric m...
The purpose of the study is to determine the effects of the compound AZD7325 as compared to lorazepam on sleepiness, concentration and brain activity.
Aims : - exploring lorazepam (0.038 mg/kg) effects, after a single oral intake, in healthy volunteers, on the neural correlates of encoding and retrieval of information during a...
The objective of this study was to investigate the bioequivalence of Mylan's lorazepam 2 mg tablets to Wyeth's Ativan 2 mg tablets following a single, oral 2 mg (1 x 2 mg) dose administere...
Medical and Biotech [MESH] Definitions
The application of TOXICOLOGY knowledge to questions of law.
A stochastic process such that the conditional probability distribution for a state at any future instant, given the present state, is unaffected by any additional knowledge of the past history of the system.
Dynamic and kinetic mechanisms of exogenous chemical and drug ABSORPTION; BIOLOGICAL TRANSPORT; TISSUE DISTRIBUTION; BIOTRANSFORMATION; elimination; and TOXICOLOGY as a function of dosage, and rate of METABOLISM. It includes toxicokinetics, the pharmacokinetic mechanism of the toxic effects of a substance. ADME and ADMET are short-hand abbreviations for absorption, distribution, metabolism, elimination and toxicology.
One of several skin tests to determine past or present tuberculosis infection. A purified protein derivative of the tubercle bacilli, called tuberculin, is introduced into the skin by scratch, puncture, or interdermal injection.
An article or portion of an article giving an account of past events or circumstances significant in a field of study, a profession, a discovery, an invention, etc. The concept of history is very wide, ranging from the dawn of time to the present. This publication type is often checked in conjunction with BIOGRAPHY.