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.
Bibliographical noteFunding Information:
This study was supported by the Korean Food and Drug Administration (KFDA) and the Korean Ministry of Science and Technology through the National Research Laboratory Program (contract number: M1-0302-00-0016). The authors would like to thank to the KFDA and the Korean Ministry of Science and Technology for their continued support.
All Science Journal Classification (ASJC) codes
- Analytical Chemistry
- Pharmaceutical Science
- Drug Discovery
- Clinical Biochemistry