Determination of tolterodine and its 5-hydroxymethyl metabolite in human plasma by hydrophilic interaction liquid chromatography-tandem mass spectrometry.
A rapid and reliable method was developed to quantitate tolterodine and its 5-hydroxymethyl metabolite in human plasma using liquid chromatography-electrospray tandem mass spectrometry. The assay was based on liquid-liquid extraction of the compounds from plasma with tert-butylmethylether and hydrophilic interaction chromatography performed on a silica column (30mmx4.6mm, 3microm particles), the mobile phase consisted of acetonitrile-20mM ammonium acetate (70:30, v/v). Quantification was through positive-ion mode and selected reaction monitoring at m/z 326-->147 for tolterodine, 342-->223 for the 5-hydroxymethyl metabolite and 260-->183 for the internal standard propranolol, respectively. The lower limit of quantitation was 49 and 46pg/ml using 0.5ml of plasma for the parent drug and its metabolite, respectively and linearity was observed up to 30ng/ml. Within-day and between-day precision expressed by relative standard deviation was less than 11% and inaccuracy did not exceed 7% at all levels. The assay was applied to the analysis of samples from a pharmacokinetic study.
Macek
Jan
J
Pharmakl s.r.o., Seydlerova 2451, CZ-15800, Prague 13, Czech Republic. macek@pharmakl.cz
Ptácek
Pavel
P
Klíma
Josef
J
D000328:Adult; D001559:Benzhydryl Compounds / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D003408:Cresols / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D008297:Male; D010665:Phenylpropanolamine / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics*; D053719:Tandem Mass Spectrometry / Q000379:methods*; D000068737:Tolterodine Tartrate; D055815:Young Adult
D001559:Benzhydryl Compounds; D003408:Cresols; D010665:Phenylpropanolamine; D000068737:Tolterodine Tartrate