Optimization and validation of the liquid chromatography coupled to tandem mass spectrometry method for assessing octreotide release from microspheres during inflammation in rabbit models.

ABSTRACT

To study the effect of acute-phase reaction (APR) of inflammation on the release of octreotide acetate microsphere (Sandostatin®, SLAR) at a clinical dose, a more sensitive liquid chromatography coupled to tandem mass spectrometry analysis method needs to be developed because of the low plasma concentrations of octreotide. Solid-phase microextraction with an Oasis® HLB µElution plate was adopted for sample preparation. Extraction recovery ranged from 65.7 % to 73.2 %, and the matrix effect was negligible. High sensitivity and an intense chromatographic peak were acquired by optimizing the chromatography and mass spectrometry conditions. The lower limit of quantitation (LLOQ) was 0.01 ng/mL based on 100 µL of plasma, and linearity ranged from 0.01 to 5.0 ng/mL. The coefficients of variations for intraday and interday precision were less than 4.4 %, and the relative error of accuracy was within 5.7 %. The validated method was successfully applied to pharmacokinetics studies of SLAR in a seven-day inflammation model of rabbits, indicating that the APR did not affected the release and pharmacokinetics of the octreotide microspheres.