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

Mei Zhang, Grant A Moore, Murray L Barclay, Evan J Begg, Mei Zhang, Grant A Moore, Murray L Barclay, Evan J Begg, Mei Zhang, Grant A. Moore, Murray L. Barclay, Evan J. Begg

文献索引：J. Chromatogr. B. Analyt. Technol. Biomed. Life Sci. 877(27) , 3025-30, (2009)

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摘要

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