title: Quantitation of pilsicainide in microscale samples of human biological fluids using liquid chromatography-tandem mass spectrometry.
abstract: This paper describes a sensitive, reliable method to determine pilsicainide (PLC) levels in microscale sample volumes of human biological fluids using liquid chromatography-tandem mass spectrometry (LC-MS/MS) with electrospray ionization (ESI). PLC and quinidine as an internal standard were extracted with diethylether from 0.1mL of alkalinized biological fluids. The extract was injected into an analytical column (l-column 2 ODS, 75mm×2.1mm i.d.). The mobile phase for separation consisted of 5mM ammonium acetate (pH 4.5)/methanol (4:1, v/v) and was delivered at a flow rate of 0.2mL/min. The drift voltage was 100V. The sampling aperture was heated at 120°C and the shield temperature was 260°C. The ion transitions used to monitor analytes were m/z 273→m/z 110 for PLC and m/z 325→m/z 79 for quinidine. The total time for chromatographic separation was less than 8min. The validated concentration ranges of this method for PLC were 5-2000ng/mL in plasma, 5-500ng/mL in ultrafiltered plasma solution, and 25-2000ng/mL in urine. Mean recoveries of PLC in plasma, ultrafiltered plasma solution, and urine were 93.2-99.7%, 91.4-100.6%, and 93.9-104.7%, respectively. Intra- and interday coefficients of variation for PLC were less than 6.0% and 4.3% in plasma, 6.1% and 3.7% in ultrafiltered plasma solution, and 5.4% and 2.5% in urine at the above concentration ranges, respectively. The lower limit of quantification for PLC in plasma, ultrafiltered plasma solution, and urine were 5ng/mL, 5ng/mL, and 25ng/mL, respectively. This method can be applied to pharmacokinetic study and therapeutic drug monitoring in special populations such as neonates, infants, and the elderly by making effective use of residual samples used for general clinical laboratory testing.
authors: Department of Hygienic Chemistry, Faculty of Pharmacy, Keio University, Tokyo, Japan.
authors: Mikiko
authors: M
authors: Shimizu
authors: Division for Evaluation and Analysis of Drug Information, Faculty of Pharmacy, Keio University, Tokyo, Japan. Electronic address: hashiguchi-ms@pha.keio.ac.jp.
authors: Masayuki
authors: M
authors: Hashiguchi
authors: Department of Cardiology, Tokyo Women's Medical University, Tokyo, Japan.
authors: Tsuyoshi
authors: T
authors: Shiga
authors: Clinical Research Tokyo Hospital, Tokyo, Japan.
authors: Koichi
authors: K
authors: Nakamura
authors: Department of Hygienic Chemistry, Faculty of Pharmacy, Keio University, Tokyo, Japan.
authors: Hiro-omi
authors: HO
authors: Tamura
authors: Division for Evaluation and Analysis of Drug Information, Faculty of Pharmacy, Keio University, Tokyo, Japan.
authors: Mayumi
authors: M
authors: Mochizuki
mesh_terms: D000328:Adult; D002853:Chromatography, Liquid / Q000379:methods*; D016903:Drug Monitoring; D006801:Humans; D008012:Lidocaine / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics / Q000652:urine; D016014:Linear Models; D008297:Male; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*; D055815:Young Adult
chemical_list: D008012:Lidocaine; C042288:pilsicainide
keywords: LC–MS/MS; Pharmacokinetics; Pilsicainide; Plasma; Therapeutic drug monitoring; Urine