Analysis and Pharmacokinetics of the New Synthetic Azulene Antiosteoporotic Compound S001-281 and its Sulphoxide Metabolite in Rats Using a LC-UV method

Abstract

In the present study an accurate and precise HPLC-UV method in rat plasma has been developed and validated for simultaneous determination of S001-281, a new synthetic azulene antiosteoporotic compound, and its sulfoxide metabolite. Separation was achieved using a reversed phase column with a mobile phase comprising acetonitrile and ammonium acetate buffer pH 6 (gradient elution) using a UV detector set at a wavelength of 308 nm. The method, applicable to 200 µL plasma, involved double extraction of the samples with diethyl ether. The absolute recovery of both the analytes was > 90%. The method was sensitive with a limit of quantitation of 25 ng/mL in rat plasma. Precision and accuracy were within the acceptable limits as indicated by bias varying from −0.11 to 16.93% and precision values ranged from 2.0 to 12.7%. Moreover, S001-281 was stable in rat plasma up to 30 days of storage at – 60 °C and after being subjected to three freeze/thaw cycles. The method was applied to generate the pharmacokinetics of S001-281 in rats after single dose oral administration.

Key words

Antiosteoporotics - Azulene derivative, biomatrices, pharmacokinetics, rat plasma, reversed phase HPLC - S001-281

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