Simultaneous quantification of abemaciclib and letrozole in rat plasma: method development, validation and...

Area of Science:

• Analytical Chemistry
• Pharmacology
• Biochemistry

Background:

• Estrogen receptor-positive breast cancer treatment often involves combined therapies.
• Abemaciclib (a CDK inhibitor) and letrozole (an aromatase inhibitor) show therapeutic potential.
• Accurate quantification of these drugs in biological matrices is essential for pharmacokinetic studies.

Purpose of the Study:

• To develop and validate a simple, simultaneous RP-HPLC bioanalytical method.
• To quantify abemaciclib and letrozole in rat plasma.
• To establish a foundation for future preclinical drug interaction studies.

Main Methods:

• Reverse-phase high-performance liquid chromatography (RP-HPLC) using a Zorbax Eclipse C18 column.
• Gradient elution with ammonium acetate and acetonitrile as the mobile phase.
• Method validation according to US FDA guidelines for selectivity, accuracy, precision, and stability.

Main Results:

• The developed RP-HPLC method achieved simultaneous quantification of abemaciclib and letrozole in rat plasma.
• The method demonstrated acceptable selectivity, accuracy (97.20-118.17%), precision (1.10-9.39%), and stability.
• The method's applicability was confirmed via a single-dose oral pharmacokinetic study in rats.

Conclusions:

• A novel and validated RP-HPLC method for simultaneous quantification of abemaciclib and letrozole in rat plasma has been successfully developed.
• This method is suitable for preclinical pharmacokinetic studies and drug-drug interaction assessments.
• This represents the first reported method for simultaneous quantification of these two drugs in any biological matrix.