title: Determination of methylnaltrexone in clinical samples by solid-phase extraction and high-performance liquid chromatography for a pharmacokinetics study.
abstract: A high-performance liquid chromatographic (HPLC) method with electrochemical detection and solid-phase extraction (SPE) using cartridges of weak cation-exchange capacity as the primary retention mechanism is described for the separation and determination of methylnaltrexone (MNTX) in small clinical samples of plasma or urine. The procedure was performed using a Phenomenex Prodigy ODS-2, 5 microm, 150x3.2 mm analytical column and 50 mM potassium acetate buffer, with 11% methanol as organic modifier at pH* 4.5 at a flow-rate of 0.5 ml/min. The detection potential was 700 mV. The six-point standard calibration curves were linear over three consecutive days in the range from 2 to 100 ng/ml. The average goodness of fit (r) was 0.9993. The lower limit of detection (LOD) and limit of quantification (LOQ) were found to be 2.0 and 5.0 ng/ml, respectively. At the LOQ, the coefficient of variation for the entire method was 8.0% and the accuracy was 10.0% (n = 10). Recovery of the drug from plasma was in the region of 94%. The method was applied to a pharmacokinetics study of methylnaltrexone after subcutaneous administration and in numerous assays of analytes in blood plasma and urine. The pharmacokinetics parameters for a single dose of 0.1 or 0.3 mg/kg in plasma were C(max) = 110 (+/-55) and 287 (+/-101) ng/ml and t(max) = 16.7 (+/-10.8) and 20.0 (+/-9.5) min, respectively. The method is simple, yet sensitive for the detection and determination of methylnaltrexone in biological samples at the level of the physiological response.
authors.affiliation: Department of Anesthesia and Critical Care, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Joachim
authors.initials: J
authors.lastname: Osinski
authors.forename: Anbao
authors.initials: A
authors.lastname: Wang
authors.forename: Ji An
authors.initials: JA
authors.lastname: Wu
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Foss
authors.forename: Chun-Su
authors.initials: CS
authors.lastname: Yuan
mesh_terms: D002138:Calibration; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006801:Humans; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D009292:Narcotic Antagonists / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D000644:Quaternary Ammonium Compounds; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D009292:Narcotic Antagonists; D000644:Quaternary Ammonium Compounds; C032257:methylnaltrexone; D009271:Naltrexone