Simultaneous determination of mexiletine and four hydroxylated metabolites in human serum by high-performance liquid chromatography and its application to pharmacokinetic studies.
A high-performance liquid chromatographic method has been developed for the simultaneous determination of mexiletine and its four hydroxylated metabolites in human serum. The method involves a single-step extraction of mexiletine, hydroxymethylmexiletine, p-hydroxymexiletine and their corresponding alcohols with diisopropyl ether-dichloromethane-propan-2-ol (2.5:1.5:0.5, v/v). Separation of the compounds on a deactivated Supelcosil LC8-DB column is accomplished by high-performance liquid chromatography with ultraviolet detection at 203 nm. Overall the recovery of each compound is reproducible and greater than 75%. The lower limit of detection is 2 ng/ml for mexiletine and its metabolites. The application of the method is shown by measuring the concentrations in serum of mexiletine and its metabolites over 24 h in a healthy volunteer after a single intravenous injection of the drug and by monitoring serum concentrations in patients receiving long-term treatment by mouth of the drug.
Paczkowski
D
D
Department of Clinical Biochemistry, National Institute of Cardiology, Warsaw, Poland.
Filipek
M
M
Mielniczuk
Z
Z
Andrzejczak
J
J
Popławska
W
W
Sitkiewicz
D
D
D002851:Chromatography, High Pressure Liquid; D006801:Humans; D006900:Hydroxylation; D013058:Mass Spectrometry; D008801:Mexiletine / Q000097:blood* / Q000378:metabolism / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D013056:Spectrophotometry, Ultraviolet
D008801:Mexiletine