title: LC-MS determination and bioavailability study of loperamide hydrochloride after oral administration of loperamide capsule in human volunteers.
abstract: The purpose of the present study was to develop a standard protocol for loperamide hydrochloride bioequivalence testing. For this purpose, a simple rapid and selective LC-MS method utilizing a single quadrupole mass spectrometer was developed and validated for the determination of loperamide hydrochloride in human plasma, and we followed this with a bioavailability study. Methyl tert-butylether (MTBE) was used to extract loperamide hydrochloride and ketoconazole (internal standard (IS)) from an alkaline plasma sample. LC separation was performed on a Zorbax RX C18 column (5 microm, 2.1 mm x 150 mm) using acetonitrile-water-formic acid (50:50:0.1 (v/v)) as a mobile phase. The retention times of loperamide hydrochloride and IS were 1.2 and 0.8 min, respectively. Quadrupole MS detection was by monitoring at m/z 477 (M + 1) corresponding to loperamide hydrochloride and at m/z 531 (M + 1) for IS. The described assay method showed acceptable precision, accuracy, linearity, stability, and specificity. The bioavailability of loperamide hydrochloride was evaluated in eight healthy male volunteers. The following pharmacokinetic parameters were elucidated after administering a single dose of four 2mg capsules of loperamide: the area under the plasma concentration versus time curve from time 0 to 72 h (AUC72 h) 19.26 +/- 7.79 ng h/ml; peak plasma concentration (Cmax) 1.18 +/- 0.37 ng/ml; time to Cmax (Tmax) 5.38 +/- 0.74 h; and elimination half-life (t1/2) 11.35 +/- 2.06 h. The developed method was successfully used to study the bioavailability of a low dose (8 mg) of loperamide hydrochloride.
authors.affiliation: National Research Laboratory of Pharmaceutical Technology, College of Pharmacy, Chungnam National University, 220 Kung-dong, Yusung-ku, Daejeon 305-764, South Korea.
authors.forename: Jin Hee
authors.initials: JH
authors.lastname: Yu
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Kim
authors.forename: Sibeum
authors.initials: S
authors.lastname: Lee
authors.forename: Sung-Joo
authors.initials: SJ
authors.lastname: Hwang
authors.forename: Won
authors.initials: W
authors.lastname: Kim
authors.forename: Cheol Jin
authors.initials: CJ
authors.lastname: Moon
mesh_terms: D000328:Adult; D000930:Antidiarrheals / Q000008:administration & dosage / Q000032:analysis* / Q000493:pharmacokinetics*; D002138:Calibration; D002214:Capsules; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D005615:Freezing; D006801:Humans; D007202:Indicators and Reagents; D008139:Loperamide / Q000008:administration & dosage / Q000032:analysis* / Q000493:pharmacokinetics*; D008297:Male; D013058:Mass Spectrometry; D015203:Reproducibility of Results; D013810:Therapeutic Equivalency
chemical_list: D000930:Antidiarrheals; D002214:Capsules; D007202:Indicators and Reagents; D008139:Loperamide