Determination of Prostaglandin E1 in dog plasma using liquid chromatography–tandem mass spectrometry and its application to a pharmacokinetic study

• An LC–MS/MS was developed and validated for the determination of PGE1 in beagle dog plasma.
• An LLOQ of 10 pg/mL was achieved.
• Indomethacin was added to plasma to avoid significant endogenous interfere.
• A simple one-step sample extraction was used followed by a short cycle time of 3 min.
• The method was applied to a pharmacokinetic study in dogs at a clinical relevant dose.

The determination of Prostaglandin (PG) E1 in plasma is challenged by its low concentration (pg/mL) and endogenous interference. An LC–MS/MS method for the determination of PGE1 in dog plasma has been developed and validated. Plasma being sampled at 4 °C and treated with indomethacin effectively inhibited interferents synthesized post-sampling. Samples were subjected to one-step extraction and separated by reversed phase HPLC with a short cycle time of 3 min. An LLOQ of 10 pg/mL was achieved with 500 μl plasma. The method was applied to a pharmacokinetic study in beagle dogs involving an intravenous infusion of 3.2 μg/kg PGE1. The half-life was recovered at 7 min. The simple, sensitive and rapid method was suitable to be applied to pharmacokinetic studies of PGE1 at clinically relevant doses.