Abstract:

Moxonidine hydrochloride is a new centrally-acting antihypertension agent that reduces blood pressure by stimulating the central α 2-adrenoceptor. The purpo se of the present study was to develop a method for loperamide hydrochloride bio equivalence testing. For this purpose, a simple rapid and selective LC-MS metho d utilizing a single quadrupole mass spectrometer was developed and validated fo r the determination of moxonidine hydrochloride in human plasma, and we followed this with a bioavailability study.Clonidine hydrochloride was used as the internal standard. After being made alka line, plasma was extracted by ethyl acetate and separated by HPLC on a reversed-phase C₁₈ column (5 μm, 4.6 mm×250 mm). HPLC-ESI-MS was performed in the selected ion monitoring (SIM) mode using target ions at m/z 242.2 for mo xonidine and m/z 230.1 for the internal standard. The retention times of moxonid ine hydrochloride and IS were 3.0 and 3.1 min, respectively. Endogenous substanc es didn't interfere the determination of moxonidine. Calibration curve was linea r over the range of 0.019 76～9.88 μg·L^-1. The limit of quantification for moxonidine hydrochloride in plasma was 0.019 76 μg·L^-1. The describ ed assay method showed acceptable precision, accuracy, linearity, stability, and specificity.A randomized crossover design was performed in 20 healthy volunteers. In the two study periods,a single 0.2 mg dose of each formulation was administered to eac h volunteer. The main pharmacokinetics parameter t_1/2, t_max and c_max were (2.86±0.33)h,(0.55±0.17)h and (1.61±0.29)μg·L^-1for the reference tablet;(2.79±0.24)h,(0.65±0.21)h and (1.62 ±0.34)μg·L^-1 for the test capsule,respectively. The relative bioavailability of the test capsule was (100.1±9.9)%. The assay was proved to be sensitive,accurate and convenient. The two formu lations were bioequivalent.