A sensitive LC–MS/MS assay to quantitate free payload Aur0101 from ADC PYX-201 in rat and monkey plasma
Feng Yin, Farah Ahsan, Jan Pinkas, Biplab Das, Frank Wang, Nancy Zheng, David Hahn, Aniruddha Amrite, Jianwen Feng, Diana Adhikari, Jack Sikora, Elizabeth Shaheen, Shawn Harriman- Medical Laboratory Technology
- Clinical Biochemistry
- General Pharmacology, Toxicology and Pharmaceutics
- General Medicine
- Analytical Chemistry
Aim: Aur0101 is a cytotoxic and small-molecule microtubule depolymerizing agent, and is the payload conjugated to antibody–drug conjugate PYX-201. Developing and validating a sensitive bioanalytical method to quantitate Aur0101 was novel and crucial in preclinical PYX-201 studies. Materials & methods: Reference standard Aur0101 and its stable isotope labelled internal standard Aur0101-d8 were used in this LC–MS/MS method. Results: This sensitive assay was validated at a lower limit of quantitation of 15 pg/ml and successfully applied to support preclinical rat and monkey toxicology studies. Preclinical plasma toxicokinetic parameters were presented. Conclusion: A sensitive and robust LC–MS/MS assay was validated for Aur0101 in rat and monkey plasma.