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
