Background: Pantoprazole and atorvastatin are often used jointly in the clinic. The drug-drug interaction
of pantoprazole and atorvastatin is worthy of being investigated.
Objective: A highly rapid, sensitive, and selective LC-MS/MS method was developed for simultaneous quantification
of pantoprazole and atorvastatin in rat plasma.
Methods: Omeprazole and atorvastatin-d5 were used as the internal standards (ISs) of pantoprazole and atorvastatin,
respectively. Simple protein precipitation was used to extract analytes from 50.0 μL plasma samples.
Results: The chromatographic separation was achieved on a C18 column and the total chromatographic run time was
3.2 min. Acquisition of mass spectrometric data was performed on a triple-quadrupole mass spectrometer in multiple-
reaction-monitoring (MRM) mode with an ESI source using the transition m/z 384→ 200 for pantoprazole and
m/z 559.4→ 440.2 for atorvastatin, respectively. The method was validated over the concentration range of 20.0 ∼
5000 ng/mL for pantoprazole and 1.00 ∼ 250 ng/mL for atorvastatin. All the validation results, including linearity,
specificity, precision, accuracy, extraction recovery, matrix effect, and stability, met the acceptance criteria as per
Conclusion: This method was successfully applied to a pharmacokinetic interaction study in Wistar rats. The results
revealed significant evidence for the drug-drug interaction between pantoprazole and atorvastatin.