[Interaction between atorvastatin and voriconazole in rat plasma: a HPLC-MS/MS-based study]

Area of Science:

• Pharmacology
• Analytical Chemistry
• Biochemistry

Background:

• Drug-drug interactions can alter pharmacokinetic profiles.
• Simultaneous quantification of multiple drugs is crucial for understanding these interactions.
• Atorvastatin and voriconazole are commonly prescribed drugs with potential for interaction.

Purpose of the Study:

• Develop and validate a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for simultaneous determination of atorvastatin and voriconazole in rat plasma.
• Investigate the pharmacokinetic changes of atorvastatin when co-administered with voriconazole in rats.

Main Methods:

• Rat plasma samples were analyzed using liquid-liquid extraction followed by HPLC-MS/MS.
• Separation was achieved on a C18 column with a gradient elution of acetonitrile and water.
• Detection was performed using selective reaction monitoring (SRM) in positive ion mode.

Main Results:

• The developed HPLC-MS/MS method demonstrated linearity, precision, and adequate recovery for both drugs.
• Co-administration of voriconazole significantly altered atorvastatin's pharmacokinetic parameters, including AUC0-24h, CLz/F, and Tmax.
• Simultaneous determination of both drugs in plasma was successfully achieved.

Conclusions:

• The established HPLC-MS/MS method is simple, rapid, and sensitive for simultaneous quantification of atorvastatin and voriconazole.
• Voriconazole significantly impacts the pharmacokinetics of atorvastatin in rats.
• Further investigation is warranted to understand the clinical implications of these pharmacokinetic alterations.