Amosulalol Hydrochloride

The pharmacokinetics and metabolism of an alpha,beta-blocker, amosulalol hydrochloride, were investigated in mice. After intravenous administration (10 mg/kg), the plasma concentration of the unchanged drug declined biphasically, with a terminal half-life of 1.1 h. The maximum plasma concentrations were reached at 0.25 h after oral administration, and then declined with apparent half-lives of 0.8-1.3 h. The systemic bioavailability of a 10-mg/kg dose was 38.7%. The area under the plasma concentration curve increased more than proportionally to the dose, which suggests metabolic saturation. After oral and intravenous administrations of (14)C-labelled amosulalol hydrochloride, 64.7% and 81.0% of the radioactivity were recovered, respectively, in the urine within 48 h. HPLC-UV and LC/MS analyses demonstrated that the major urinary metabolite was the glucuronide of M-2 (desmethyl metabolite at the o-methoxyphenoxy group) followed by M-5, the M-3 glucuronide, and the M-4 glucuronide, in that order. In the bile sample, amosulalol carbamoyl glucuronide was found as a new metabolite of this drug.

Amosulalol is an antihypertensive drug with selective postsynaptic alpha 1 and non-selective beta blocking effects. A simple solid-phase extraction and high-performance liquid chromatographic (HPLC) method has been developed and validated for the quantitative determination of amosulalol in human plasma. A reversed phase C18 column was used for the separation of amosulalol and ethyl paraben (internal standard) with a mobile phase composed of 0.025 M phosphate buffer (pH 6.0).acetonitrile (73:27, v/v) at a flow rate of 1.5 mL/min. The ultraviolet detector was operated at the 272 nm wavelength. Intra- and inter-day precision and accuracy were acceptable for all quality control samples including the lower limit of quantification of 30 ng/mL. Recovery of amosulalol from human plasma was >95.6%. Amosulalol was stable in human plasma under various storage conditions. This method was used successfully for a pharmacokinetic study in plasma after oral administration of a single 20 mg dose of amosulalol hydrochloride to 16 healthy volunteers.