Development and validation of HPLC-UV and HPLC-MS/MS methods for ML-210 quantification

Area of Science:

• Analytical Chemistry
• Pharmacology
• Biochemistry

Background:

• ML-210, a GPX-4 inhibitor, shows promise for cancer therapy.
• Lack of validated methods hinders ML-210 pharmacokinetic and stability studies.

Purpose of the Study:

• Develop and validate analytical and bioanalytical methods for ML-210 quantification.
• Establish methods for formulation, cell culture medium, and plasma analysis.
• Support pharmacokinetic and preclinical investigations of ML-210.

Main Methods:

• HPLC-UV method for ML-210 in intravenous formulations.
• HPLC-MS/MS method for ML-210 in DMEM and mouse plasma.
• Validation according to ICH Q2(R1) and FDA bioanalytical guidelines.

Main Results:

• Validated HPLC-UV and HPLC-MS/MS methods demonstrated high specificity, accuracy, and precision.
• ML-210 stability confirmed for 6 months at -20°C and ~2h in plasma at 37°C.
• In vivo pharmacokinetic study in mice showed rapid ML-210 decline with a ~300 min half-life.

Conclusions:

• Validated analytical methods provide a reliable platform for ML-210 quantification.
• These methods are essential for future pharmacokinetic and preclinical research.
• Enables further investigation into ML-210's therapeutic potential in cancer.