Online citations, reference lists, and bibliographies.

Quantification Of Total And Unbound Concentrations Of Lorazepam, Oxazepam And Temazepam In Human Plasma By Ultrafiltration And LC-MS/MS.

Helle S Larsen, Paul K.L. Chin, Evan J. Begg, Berit P. Jensen
Published 2011 · Chemistry, Medicine

Cite This
Download PDF
Analyze on Scholarcy
Share
BACKGROUND A fast and sensitive assay for quantifying total and unbound concentrations of lorazepam (Lzp), oxazepam (Ozp) and temazepam (Tzp) in human plasma was needed for a plasma protein binding study. RESULTS Plasma samples were precipitated with acetonitrile for determination of total concentrations or subjected to ultrafiltration for determination of unbound concentrations. An LC-MS/MS assay was developed with an Allure® PFP propyl column and a mobile phase of 35% acetonitrile/0.1% formic acid over 4.5 min and ESI+-MS/MS detection. Matrix effects were negligible in plasma and approximately 70% in ultrafiltrate but were accounted for by the internal standards Lzp-d₄, Ozp-d₅ and Tzp-d₅. The assay was validated for total concentrations of 10-100 ng/ml Lzp, 200-2000 ng/ml Ozp and 100-1000 ng/ml Tzp, and for unbound concentrations of 1-10 ng/ml Lzp, 20-200 ng/ml Ozp and 10-100 ng/ml Tzp. Precision was <14% CV and accuracy was 96-110% throughout the calibration range. The mean precision of triplicate analysis of 60 study samples was <4% CV for total and <8% CV for unbound concentrations. CONCLUSION A fast and sensitive assay was developed and validated. It has been applied successfully to a protein binding study.
This paper references
10.1007/s11095-007-9291-7
Quantitative Bioanalytical Methods Validation and Implementation: Best Practices for Chromatographic and Ligand Binding Assays
C. T. Viswanathan (2007)
10.1002/JMS.824
Development and validation of a liquid chromatographic/electrospray ionization mass spectrometric method for the quantitation of prazepam and its main metabolites in human plasma.
P. Valavani (2005)
10.7326/0003-4819-84-4-420
Normal disposition of oxazepam in acute viral hepatitis and cirrhosis.
H. Shull (1976)
10.1016/J.JCHROMB.2004.12.038
Liquid chromatography-electrospray ionisation mass spectrometry for the determination of nine selected benzodiazepines in human plasma and oral fluid.
Ó. Quintela (2005)
10.1002/jps.2600700208
Ultrafiltration in serum protein binding determinations.
J. B. Whitlam (1981)
10.4155/bio.09.117
Matrix effect elimination during LC-MS/MS bioanalytical method development.
Cynthia Côté (2009)
10.1016/j.tox.2004.06.010
Clarke’s Analysis of Drugs and Poisons (3rd Edition, 2004): A.C. Moffat, M.D. Osselton, B. Widdop (Eds.), Pharmaceutical Press, London, UK, Vol. 1 (564 pp.), Vol. 2 (1935 pp.) in a durable slipcase, £350/US$545, ISBN 0-85369-473-7
Hans Marquardt (2004)
Melmon and Morrelli’s Clinical Pharmacology (4th Edition)
JA Abishenganaden (2000)
10.1002/jps.2600701004
Effect of age and gender on disposition of temazepam.
M. Divoll (1981)
10.1002/jps.2600681034
Plasma binding of benzodiazepines in humans.
R. Johnson (1979)
10.1002/JMS.599
Screening, library-assisted identification and validated quantification of 23 benzodiazepines, flumazenil, zaleplone, zolpidem and zopiclone in plasma by liquid chromatography/mass spectrometry with atmospheric pressure chemical ionization.
C. Kratzsch (2004)
10.1016/J.JPBA.2005.02.024
A fast and sensitive liquid chromatographic-tandem mass spectrometric method for assay of lorazepam and application to pharmacokinetic analysis.
Hailin Zhu (2005)
10.2165/00003088-198712010-00004
Plasma Protein Binding of Drugs in the Elderly
S. J. Wallace (1987)
10.1093/clinchem/28.7.1726
Free drug concentrations are constant in serial fractions of plasma ultrafiltrate.
R. Judd (1982)
10.1016/S1570-0232(03)00040-0
Fast analysis using monolithic columns coupled with high-flow on-line extraction and electrospray mass spectrometric detection for the direct and simultaneous quantitation of multiple components in plasma.
H. Zeng (2003)
10.1023/A:1024406221962
Modulation of Nonspecific Binding in Ultrafiltration Protein Binding Studies
K. Lee (2004)
10.1038/clpt.1981.241
Renal disease, age, and oxazepam kinetics
T. Murray (1981)
10.1097/FTD.0b013e3181817318
Determination of Unbound Antiretroviral Drug Concentrations by a Modified Ultrafiltration Method Reveals High Variability in the Free Fraction
A. Fayet (2008)
10.1002/1097-0231(20001115)14:21<2061::AID-RCM135>3.0.CO;2-8
A study of the electrospray ionisation of pharmacologically significant 1,4-benzodiazepines and their subsequent fragmentation using an ion-trap mass spectrometer.
W. F. Smyth (2000)
10.1111/j.2042-7158.1982.tb04201.x
Effect of age and sex on lorazepam protein binding
M. Divoll (1982)
10.2165/00003088-199630060-00003
Measurement and Analysis of Unbound Drug Concentrations
Jennifer D. Wright (1996)
Oxazepam kinetics: effects of age and sex.
D. Greenblatt (1980)
10.1016/S0003-2670(03)00304-0
Simple method for the determination of benzodiazepines in human body fluids by high-performance liquid chromatography–mass spectrometry
X. Lee (2003)
Methodologic factors influencing plasma binding of alpha-1-acid glycoprotein-bound and albumin-bound drugs.
D. Morse (1985)
10.1016/j.jpba.2008.07.014
A new approach to the application of solid phase extraction disks with LC-MS/MS for the analysis of drugs on a 96-well plate format.
E. Cudjoe (2009)



This paper is referenced by
10.1093/jat/bkz101
An Experimental Pharmacokinetics Study of Diazepam and Its Metabolites in Oral Fluid of Chinese Population.
L. Wang (2020)
10.1002/bmc.3401
Study on the interaction of plasma protein binding rate between edaravone and taurine in human plasma based on HPLC analysis coupled with ultrafiltration technique.
Dao-Quan Tang (2015)
10.4037/aacnacc2017386
Considerations for Medication Management and Anticoagulation During Continuous Renal Replacement Therapy
A. Thompson (2017)
10.5897/AJPP2013.3416
Clinical consequences of anxiolytics binded to plasma proteins
H. Olguín (2013)
10.1016/B978-0-12-800634-4.00035-4
Assays for Benzodiazepines
Elisabetta Bertol (2016)
10.1002/9781118671276.CH25
LC‐MS Bioanalysis of Unbound Drugs in Plasma and Serum
T. W. de Boer (2013)
10.2478/ACPH-2019-0015
Prediction of drug-drug plasma protein binding interactions of resveratrol in combination with celecoxib and leflunomide by molecular docking combined with an ultrafiltration technique
Mohammed Al-Bratty (2020)
10.1007/s13318-020-00614-8
Study on the Pharmacokinetics of Diazepam and Its Metabolites in Blood of Chinese People
Le-le Wang (2020)
10.1111/j.1365-2125.2011.04036.x
Adult age and ex vivo protein binding of lorazepam, oxazepam and temazepam in healthy subjects.
P. Chin (2011)
Determination of the Plasma Protein Binding of New Psychoactive Substances
M. Meyer (2018)
10.1016/j.jpba.2016.09.021
Pharmaceutical applications of affinity-ultrafiltration mass spectrometry: Recent advances and future prospects.
H. Wei (2016)
10.1002/9781119274315.CH3
Equilibrium Dialysis, Ultracentrifugation, and Ultrafiltration in LC‐MS Bioanalysis
T. W. de Boer (2019)
10.2478/acph-2019-0015
Prediction of drug-drug plasma protein binding interactions of resveratrol in combination with celecoxib and leflunomide by molecular docking combined with an ultrafiltration technique
Peng Zhou (2019)
10.1039/C8RA07153E
Effect of Ling-Gui-Zhu-Gan decoction major components on the plasma protein binding of metoprolol using UPLC analysis coupled with ultrafiltration
Peng Zhou (2018)
10.1016/J.TRAC.2013.01.004
High-throughput solid-phase microextraction in multi-well-plate format
D. Vuckovic (2013)
Semantic Scholar Logo Some data provided by SemanticScholar