Validated method for the quantification of baclofen in human plasma using solid-phase extraction and liquid chromatography–tandem mass spectrometry
File(s)
Accepted version
Author(s)
Type
Journal Article
Abstract
A highly sensitive and fully validated method was developed for the quantification of baclofen in human plasma. After adjusting the pH of the plasma samples using a phosphate buffer solution (pH 4), baclofen was purified using mixed mode (C8/cation exchange) solid-phase extraction (SPE) cartridges. Endogenous water-soluble compounds and lipids were removed from the cartridges before the samples were eluted and concentrated. The samples were analyzed using triple-quadrupole
liquid chromatography–tandem mass spectrometry (LC–MS-MS) with triggered dynamic multiple reaction monitoring mode for simultaneous quantification and confirmation. The assay was linear from 25 to 1,000 ng/mL (r2 > 0.999; n = 6). Intraday (n = 6) and interday (n = 15) imprecisions (% relative standard deviation) were <5%, and the average recovery was 30%. The limit of detection of the method was 5 ng/mL, and the limit of quantification was 25 ng/mL. Plasma samples from healthy
male volunteers (n = 9, median age: 22) given two single oral doses of baclofen (10 and 60 mg) on nonconsecutive days were analyzed to demonstrate method applicability.
liquid chromatography–tandem mass spectrometry (LC–MS-MS) with triggered dynamic multiple reaction monitoring mode for simultaneous quantification and confirmation. The assay was linear from 25 to 1,000 ng/mL (r2 > 0.999; n = 6). Intraday (n = 6) and interday (n = 15) imprecisions (% relative standard deviation) were <5%, and the average recovery was 30%. The limit of detection of the method was 5 ng/mL, and the limit of quantification was 25 ng/mL. Plasma samples from healthy
male volunteers (n = 9, median age: 22) given two single oral doses of baclofen (10 and 60 mg) on nonconsecutive days were analyzed to demonstrate method applicability.
Date Issued
2016-03-01
Date Acceptance
2015-10-05
Citation
Journal of Analytical Toxicology, 2016, 40 (2), pp.117-123
ISSN
0146-4760
Publisher
Oxford University Press (OUP): Policy F
Start Page
117
End Page
123
Journal / Book Title
Journal of Analytical Toxicology
Volume
40
Issue
2
Copyright Statement
© 2015 Oxford University Press. This is a pre-copy-editing, author-produced version of an article accepted for publication in Journal of Analytical Toxicology following peer review. The definitive publisher-authenticated version Limon Khatun Nahar, Rosa Elena Cordero, David Nutt, Anne Lingford-Hughes, Samuel Turton, Claire Durant, Sue Wilson, Sue Paterson; Validated Method for the Quantification of Baclofen in Human Plasma Using Solid-Phase Extraction and Liquid Chromatography–Tandem Mass Spectrometry, Journal of Analytical Toxicology, Volume 40, Issue 2, 1 March 2016, Pages 117–123 is available online at: https://doi.org/10.1093/jat/bkv125
Sponsor
Medical Research Council (MRC)
Grant Number
G1002226
Subjects
Science & Technology
Physical Sciences
Life Sciences & Biomedicine
Chemistry, Analytical
Toxicology
Chemistry
CEREBROSPINAL-FLUID
ACID BACLOFEN
ULTRAVIOLET DETECTION
BIOLOGICAL-MATERIAL
URINE
LIORESAL
INGESTION
Adult
Baclofen
Chromatography, High Pressure Liquid
Deuterium
GABA-B Receptor Agonists
Humans
Hydrogen-Ion Concentration
Limit of Detection
Male
Solid Phase Extraction
Tandem Mass Spectrometry
Young Adult
0301 Analytical Chemistry
1115 Pharmacology And Pharmaceutical Sciences
Analytical Chemistry
Publication Status
Published
Date Publish Online
2015-11-04