LC-MS determination and bioavailability study of loperamide hydrochloride after oral administration of loperamide capsule in human volunteers

Jin Hee Yu, Hye Jin Kim, Sibeum Lee, Sung Joo Hwang, Won Kim, Cheol Jin Moon

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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 C 18 column (5 μm, 2.1 mm × 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 2 mg capsules of loperamide: the area under the plasma concentration versus time curve from time 0 to 72 h (AUC 72 h) 19.26 ± 7.79 ng h/ml; peak plasma concentration (C max) 1.18 ± 0.37 ng/ml; time to C max (T max) 5.38 ± 0.74 h; and elimination half-life (t 1/2) 11.35 ± 2.06 h. The developed method was successfully used to study the bioavailability of a low dose (8 mg) of loperamide hydrochloride.

Original languageEnglish
Pages (from-to)421-427
Number of pages7
JournalJournal of Pharmaceutical and Biomedical Analysis
Issue number2
Publication statusPublished - 2004 Oct 29


All Science Journal Classification (ASJC) codes

  • Analytical Chemistry
  • Pharmaceutical Science
  • Drug Discovery
  • Spectroscopy
  • Clinical Biochemistry

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