The validation of an LC–MS/MS assay for perhexiline and major hydroxy metabolites, and its application to therapeutic monitoring in patient plasma. (July 2017)

• Record Type: Journal Article
• Authors: Camilleri, Patrick; Zhang, Duxi; Midei, Mark; Daly, William; Copp, James; Flinn, Cindy; Luongo, Carl; Shamszad, Pirouz
• Is Part Of: Bioanalysis. Volume 9:Number 13(2017)
• Page Start: 1011
• Page End: 1025
• Publication Date: 2017-07
• Subjects: assay validation -- perhexiline. hydroxy metabolites -- LC–MS/MS -- novel internal standards -- therapeutic monitoring; Drugs -- Analysis -- Periodicals; 615.19005
• DOI: 10.4155/bio-2017-0068
• Languages: English
• ISSNs: 1757-6180

Abstract

Aim: Perhexiline (PEX), being developed to treat hypertrophic cardiomyopathy, is toxic at levels above the therapeutic range. Plasma level monitoring is therefore essential. The absence of a UV-absorbing chromophore has in the past required quantitative analysis of PEX in plasma using lengthy derivatization methods, followed by HPLC and fluorescence detection. The routine and urgent analysis of a large number of patient plasma samples necessitates faster and reliable analytical methodology.Results: An LC–MS/MS method, using two novel internal standards, has been validated for the quantitative measurement of PEX and its major hydroxy metabolites in human plasma.Conclusion: The assay has been applied to therapeutic drug monitoring (TDM), where PEX and the ratio of the drug to cis -hydroxy perhexiline, were measured at designated intervals.