Enhanced LC-MS/MS analysis of alogliptin and pioglitazone in human plasma: Applied to a preliminary pharmacokinetic study

- Enhanced UPLC-MS/MS Determination of alogliptin and pioglitazone in human plasma.
- The First Pharmacokinetic study for the drugs on Egyptian volunteers.
- The First method with full details regarding extraction and bioanalysis.
- As per FDA guidelines, a detailed validation of the method was carried out.
- Rapid analysis of high number of human plasma samples per day.

A new fast LC-MS/MS method was developed for determination of alogliptin and pioglitazone in human plasma. Linearity ranges of 10-400 ng mL−1 for alogliptin and 25-2000 ng mL−1 for pioglitazone, were found to be suitable for their bioanalysis covering the Cmin and Cmax values of the drugs. Direct precipitation technique was used for simultaneous extraction of the drugs successfully from human plasma samples. Chromatographic separation was achieved on a BEH C18 column (50 mm × 2.1 mm, 1.7 μm) with 0.1% aqueous formic acid: acetonitrile (40:60, v/v) at a flow rate of 0.3 mL min−1. The validated method was applied to a preliminary pharmacokinetic study on human volunteers. Monitoring the transition pairs of m/z 340.18 to 116.08 for alogliptin and m/z 356.99 to 133.92 for pioglitazone, using triple quadrupole mass spectrometer with multiple reaction monitoring, was achieved in the positive mode. The validated method is accurate and suitable for further clinical applications and possible bioequivalence studies.