Micro-solid phase extraction and LC-MS3 for the determination of triptorelin in rat plasma and application to a pharmacokinetic study

Triptorelin is a synthetic decapeptide used for the treatment of prostate cancer. Attempts to determine triptorelin in clinical use by liquid chromatography-tandem mass spectrometry with multiple reaction monitoring have encountered problems due to its low concentration in plasma (pg/mL) and interference from endogenous peptides. We have overcome these issues using micro-solid phase extraction (mu-SPE) on Oasis (R) HLB 96-well mu Elution plates followed by LC-MS3. Sample preparation by mu-SPE achieved sample concentration without the need for evaporation and reconstitution steps. Detection by LC-MS3 showed no significant matrix interference at the retention time of analyte and achieved high sensitivity (lower limit of quantitation 10 pg/mL) and good linearity in the range 10-3000 pg/mL. The method was successfully applied to a pharmacokinetic study in rat involving a single intramuscular injection of a formulation of triptorelin acetate biodegradable microspheres. (C) 2018 Elsevier B.V. All rights reserved.