title: Determination of perhexiline and hydroxyperhexiline in plasma by liquid chromatography-mass spectrometry.
abstract: A method for the quantitative determination of perhexiline and its main hydroxylated metabolites in human plasma, based on liquid chromatography-mass spectrometry (LC-MS), was developed. The method used protein precipitation with acetonitrile followed by dilution with water and subsequent direct injection of the extract into the LC-MS system. Hexadiline was used as internal standard and the intra-assay coefficients of variation were <or=5% for perhexiline and cis-hydroxyperhexiline over the target concentration range in patients. The lower limits of quantification were 0.005mg/l for perhexiline and 0.015mg/l for cis-hydroxyperhexiline, and the measuring ranges were from 0.05 to 3.0 and from 0.2 to 6.0mg/l, respectively. The method was compared with an established HPLC method with fluorescence detection and the correlation between the methods was close to 1 for both compounds. The predominant form of hydroxyperhexiline in 87% of the patient samples was found to be one of the diastereomeric pairs of cis-hydroxyperhexiline. In patients not forming this metabolite, trans-hydroxyperhexiline could be detected. We conclude that the present LC-MS method is suitable for use in a clinical routine laboratory.
authors.affiliation: Department of Medicine, Division of Clinical Pharmacology, Karolinska Hospital & Institute, SE-17176 Stockholm, Sweden. olof.beck@ks.se
authors.forename: O
authors.initials: O
authors.lastname: Beck
authors.forename: N
authors.initials: N
authors.lastname: Stephanson
authors.forename: R G
authors.initials: RG
authors.lastname: Morris
authors.forename: B C
authors.initials: BC
authors.lastname: Sallustio
authors.forename: P
authors.initials: P
authors.lastname: Hjemdahl
mesh_terms: D002317:Cardiovascular Agents / Q000097:blood*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006801:Humans; D007536:Isomerism; D013058:Mass Spectrometry / Q000379:methods*; D010480:Perhexiline / Q000031:analogs & derivatives* / Q000097:blood*; D012015:Reference Standards
chemical_list: D002317:Cardiovascular Agents; C493998:hydroxyperhexiline; D010480:Perhexiline