Determination of perhexiline and its metabolite hydroxyperhexiline in human plasma by liquid chromatography/tandem mass spectrometry. 2009

Mei Zhang, and Grant A Moore, and Murray L Barclay, and Evan J Begg
Department of Medicine, University of Otago-Christchurch, Christchurch, New Zealand. mei.zhang@cdhb.govt.nz

Perhexiline is a drug that is used for treatment of moderate to severe angina pectoris that has not responded to other treatment. It has a low therapeutic index, and saturable metabolism that is also subject to genetic polymorphism (CYP2D6). Concentration monitoring of the parent drug and its major metabolite is considered necessary to optimise efficacy and reduce the risk of hepatotoxicity and neuropathy. A rapid, simple and sensitive liquid chromatography/tandem mass spectrometry (LC-MS/MS) assay was developed for the determination of perhexiline and its metabolite cis-hydroxyperhexiline in human plasma. After proteins were precipitated with acetonitrile, perhexiline, the major metabolite cis-hydroxyperhexiline and nordoxepin as the internal standard were resolved on a phenyl-hexyl column using gradient elution of 0.05% formic acid and methanol. The three compounds were detected using electrospray ionisation in the positive mode. Standard curves were linear over the concentration range 10-2000microg/L (r>0.999), bias was <or=+/-10%, intra- and inter-day coefficients of variation (imprecision) were <or=8.1%, and the limit of quantification was 10microg/L for both perhexiline and hydroxyperhexiline. The assay is being used successfully in clinical practice to enhance the safe and effective use of perhexiline.

UI MeSH Term Description Entries
D010480 Perhexiline 2-(2,2-Dicyclohexylethyl)piperidine. Coronary vasodilator used especially for angina of effort. It may cause neuropathy and hepatitis. Perhexilene
D002853 Chromatography, Liquid Chromatographic techniques in which the mobile phase is a liquid. Liquid Chromatography
D004316 Doxepin A dibenzoxepin tricyclic compound. It displays a range of pharmacological actions including maintaining adrenergic innervation. Its mechanism of action is not fully understood, but it appears to block reuptake of monoaminergic neurotransmitters into presynaptic terminals. It also possesses anticholinergic activity and modulates antagonism of histamine H(1)- and H(2)-receptors. Apo-Doxepin,Aponal,Deptran,Desidox,Doneurin,Doxepia,Doxepin Hydrochloride,Doxepin Hydrochloride, Cis-Trans Isomer Mixture (approximately 1:5),Doxepin beta,Doxepin-RPh,Espadox,Mareen,Novo-Doxepin,Prudoxin,Quitaxon,Sinequan,Sinquan,Xepin,Zonalon,Apo Doxepin,ApoDoxepin,Doxepin RPh,Hydrochloride, Doxepin,Novo Doxepin
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D012680 Sensitivity and Specificity Binary classification measures to assess test results. Sensitivity or recall rate is the proportion of true positives. Specificity is the probability of correctly determining the absence of a condition. (From Last, Dictionary of Epidemiology, 2d ed) Specificity,Sensitivity,Specificity and Sensitivity
D015203 Reproducibility of Results The statistical reproducibility of measurements (often in a clinical context), including the testing of instrumentation or techniques to obtain reproducible results. The concept includes reproducibility of physiological measurements, which may be used to develop rules to assess probability or prognosis, or response to a stimulus; reproducibility of occurrence of a condition; and reproducibility of experimental results. Reliability and Validity,Reliability of Result,Reproducibility Of Result,Reproducibility of Finding,Validity of Result,Validity of Results,Face Validity,Reliability (Epidemiology),Reliability of Results,Reproducibility of Findings,Test-Retest Reliability,Validity (Epidemiology),Finding Reproducibilities,Finding Reproducibility,Of Result, Reproducibility,Of Results, Reproducibility,Reliabilities, Test-Retest,Reliability, Test-Retest,Result Reliabilities,Result Reliability,Result Validities,Result Validity,Result, Reproducibility Of,Results, Reproducibility Of,Test Retest Reliability,Validity and Reliability,Validity, Face
D016014 Linear Models Statistical models in which the value of a parameter for a given value of a factor is assumed to be equal to a + bx, where a and b are constants. The models predict a linear regression. Linear Regression,Log-Linear Models,Models, Linear,Linear Model,Linear Regressions,Log Linear Models,Log-Linear Model,Model, Linear,Model, Log-Linear,Models, Log-Linear,Regression, Linear,Regressions, Linear
D053719 Tandem Mass Spectrometry A mass spectrometry technique using two (MS/MS) or more mass analyzers. With two in tandem, the precursor ions are mass-selected by a first mass analyzer, and focused into a collision region where they are then fragmented into product ions which are then characterized by a second mass analyzer. A variety of techniques are used to separate the compounds, ionize them, and introduce them to the first mass analyzer. For example, for in GC-MS/MS, GAS CHROMATOGRAPHY-MASS SPECTROMETRY is involved in separating relatively small compounds by GAS CHROMATOGRAPHY prior to injecting them into an ionization chamber for the mass selection. Mass Spectrometry-Mass Spectrometry,Mass Spectrometry Mass Spectrometry,Mass Spectrometry, Tandem

Related Publications

Mei Zhang, and Grant A Moore, and Murray L Barclay, and Evan J Begg
October 2015, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences,
Mei Zhang, and Grant A Moore, and Murray L Barclay, and Evan J Begg
December 2005, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences,
Mei Zhang, and Grant A Moore, and Murray L Barclay, and Evan J Begg
March 2017, Yao xue xue bao = Acta pharmaceutica Sinica,
Mei Zhang, and Grant A Moore, and Murray L Barclay, and Evan J Begg
August 2016, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences,
Mei Zhang, and Grant A Moore, and Murray L Barclay, and Evan J Begg
May 2001, Journal of chromatography. B, Biomedical sciences and applications,
Mei Zhang, and Grant A Moore, and Murray L Barclay, and Evan J Begg
November 2000, Journal of mass spectrometry : JMS,
Mei Zhang, and Grant A Moore, and Murray L Barclay, and Evan J Begg
July 2014, Yao xue xue bao = Acta pharmaceutica Sinica,
Mei Zhang, and Grant A Moore, and Murray L Barclay, and Evan J Begg
June 2004, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences,
Mei Zhang, and Grant A Moore, and Murray L Barclay, and Evan J Begg
December 2001, Biomedical chromatography : BMC,
Mei Zhang, and Grant A Moore, and Murray L Barclay, and Evan J Begg
November 2019, Journal of pharmaceutical and biomedical analysis,
Copied contents to your clipboard!