Quantitative assay of lorazepam and its metabolite glucuronide by reverse-phase liquid chromatography-tandem mass spectrometry in human plasma and urine samples

Papini, Olga; Bertucci, Carlo; Cunha, Sérgio Pereira da; Santos, Neife Aparecida Guinaim dos; Lanchote, Vera Lúcia

doi:10.1016/j.jpba.2005.07.033

Cited by 18 publications

(7 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The method can be applied to both plasma and urine and has a LOQ of 0.2 ng/mL; the sample pre-treatment procedure is based on LLE with tert-butyl ether and needs 1 mL of sample for one analysis. The metabolite is quantified as the difference between total and nonglucuronidated lorazepam, after hydrolysis with β-glucuronidase [92]. Nitrazepam is used as the IS.…”

Section: -Analytical Methodsmentioning

confidence: 99%

Benzodiazepine Metabolism: An Analytical Perspective

Mandrioli¹,

Mercolini²,

Raggi

2008

CDM

140

View full text Add to dashboard Cite

Benzodiazepines are currently among the most frequently prescribed drugs all over the world. They act as anxiolytics, sedatives, hypnotics, amnesics, antiepileptics and muscle relaxants. Despite their common chemical scaffold, these drugs differ in their pharmacokinetic and metabolic properties. In particular, they are biotransformed by different cytochrome P450 isoforms and also by different UDP-glucuronosyltransferase subtypes. The most important studies on the metabolic characteristics of several 1,4-benzodiazepines, carried out from 1998 onwards, are reported and briefly discussed in this review. Moreover, the analytical methods related to these studies are also described and commented upon and their most important characteristics are highlighted. Most methods are based on liquid chromatography, which provides wide applicability and good analytical performance granting high precision, accuracy and feasibility. Mass spectrometry is gaining widespread acceptance, particularly if the matrix is very complex and variable, such as human or animal blood. However, spectrophotometric detection is still used for this purpose and can grant sufficient selectivity and sensitivity when coupled to suitable sample pre-treatment procedures. A monograph is included for each of the following benzodiazepines: alprazolam, bromazepam, brotizolam, clotiazepam, diazepam, etizolam, flunitrazepam, lorazepam, midazolam, oxazepam and triazolam.

show abstract

Section: -Analytical Methodsmentioning

confidence: 99%

Benzodiazepine Metabolism: An Analytical Perspective

Mandrioli¹,

Mercolini²,

Raggi

2008

CDM

140

View full text Add to dashboard Cite

show abstract

“…Papini et al () developed an enantioselective assay of lorazepam in plasma and urine using a chiral column. The enantioselective LC‐MS/MS assay allowed them to separate the enantiomers and to verify the stereochemical instability of lorazepam.…”

Section: Lc Separationmentioning

confidence: 99%

Analyses of benzodiazepines and their metabolites in various biological matrices by LC-MS(/MS)

Nakamura

2011

Biomed. Chromatogr.

View full text Add to dashboard Cite

Benzodiazepines are among the most frequently prescribed drugs due to their sedative, hypnotic, anxiolytic, muscle relaxant and antiepileptic properties. Because of the high consumption of benzodiazepines worldwide, this class of drugs and their metabolites are frequently present in both clinical and forensic cases. For these reasons, the analysis of benzodiazepines and their metabolites in biological fluids is of great interest to clinicians and forensic toxicologists. This paper reviews procedures for multi-analyte single-stage (LC-MS) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) using different mass analyzers for the screening, identification and/or quantification of drugs, poisons and/or their metabolites in blood, plasma, serum or urine published since 2001. Basic information about the biosamples assayed, work-up, LC column, mobile phase, ionization type, mass spectral detection mode, matrix effects and validation data for each procedure is summarized. The feasibility of using LC-MS(/MS) techniques to identify and quantify benzodiazepines and their metabolites is also discussed.

show abstract

“…They have sedative, hypnotic, anxiolytic, muscle relaxant, anticonvulsant action and are used to treat anxiety, insomnia, agitation, seizures and muscle spam. [5][6][7][8][9] Illicit use and misuse of benzodiazepine drugs is related to sexual assault and robbery crimes, suicides, and reducing after-effects of LSD, amphetamine or Ecstasy. This generates an increased frequency of the chloride channel opening and implicitly to appearance of the tranquilizing effect.…”

Section: Introductionmentioning

confidence: 99%

“…Benzodiazepines and zolpidem have toxicological and forensic potential due to drug overdose, abuse and misuse, being analyzed, among others from biological samples like plasma, serum, saliva, urine, or hair in the frame of clinical, toxicological, or forensic studies. [5][6][7][8][9] Illicit use and misuse of benzodiazepine drugs is related to sexual assault and robbery crimes, suicides, and reducing after-effects of LSD, amphetamine or Ecstasy. [4,10,11] Various methods for determination of benzodiazepines and zolpidem from pharmaceutical formulations and biological samples from living or deceased abusers, have been reported including high-performance liquid chromatography (HPLC), [12] gas chromatography (GC), [13] gas chromatography-mass spectrometry (GC-MS), [14,15] gas chromatography-tandem mass spectroscopy (GC-MS/MS), [16] liquid chromatography-mass spectrometry (LC-MS), [17,18] and liquid chromatography-tandem mass spectrometry (LC-MS/MS).…”

Section: Introductionmentioning

confidence: 99%

Simultaneous ESI‐APCI(+) ionization and fragmentation pathways for nine benzodiazepines and zolpidem using single quadrupole LC‐MS

Galaon

Vacaresteanu

Anghel

et al. 2013

Drug Testing and Analysis

View full text Add to dashboard Cite

Nine important 1,4-benzodiazepines and zolpidem were characterized by liquid chromatography-mass spectrometry using a multimode ionization source able to generate ions using both electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI), and a single quadrupole mass analyzer. An optimum chromatographic separation was applied for all target compounds in less than 8 minutes using a Zorbax Eclipse Plus column (100 x 4.6 mm, 3.5 μm) kept at 35°C and a 0.3% HCOOH/ ACN/IPA (61:34:5) mobile phase pumped at 1 ml/min. Optimization of LC-MS method generated low limit of quantitation (LOQ) values situated in the range 0.3-20.5 ng/ml. Comparison between differences in method sensitivity, under specified chromatographic conditions, when using ESI-only, APCI-only, and simultaneous ESI-APCI ionization with such a multimode source was discussed. Mixed ESI-APCI(+) mode proved to be the most sensitive ionization generating an average 35% detector response increase compared to ESI-only ionization and 350% detector response increase with respect to APCI-only ionization. Characterization of the nine benzodiazepines and zolpidem concerning their MS fragmentation pathway following 'in-source' collision-induced dissociation is discussed in detail and some general trends regarding these fragmentations are set.

show abstract

Quantitative assay of lorazepam and its metabolite glucuronide by reverse-phase liquid chromatography-tandem mass spectrometry in human plasma and urine samples

Cited by 18 publications

References 20 publications

Benzodiazepine Metabolism: An Analytical Perspective

Benzodiazepine Metabolism: An Analytical Perspective

Analyses of benzodiazepines and their metabolites in various biological matrices by LC-MS(/MS)

Simultaneous ESI‐APCI(+) ionization and fragmentation pathways for nine benzodiazepines and zolpidem using single quadrupole LC‐MS

Contact Info

Product

Resources

About