A highly selective and sensitive LC-MS/HRMS assay for quantifying coproporphyrins as organic anion-transporting
Ragu Ramanathan1, Amanda J King-Ahmad1, Christopher L Holliman1
1Research & Development, Pharmacokinetics, Dynamics & Metabolism, Pfizer Inc., 445 Eastern Point Road, Groton, CT 06340, USA.
Aim:
Coproporphyrin-I (CP-I) and coproporphyrin-III (CP-III) in plasma and urine have been proposed as biomarkers for assessing drug-drug interactions involving hepatic drug transporters such as organic anion-transporting peptides (OATP), 1B1 and 1B3. Materials & methods: Plasma and urine extracts were analyzed for CP-I/CP-III using a TripleTOF API6600 mass spectrometer. Results: Previously unreported, CP-I/CP-III doubly charged ions (m/z 328.14) were used as precursor ions to improve the assay sensitivity and selectivity over the singly charged precursor ions (m/z 655.28). Levels of CP-I and CP-III measured ranged 0.45-1.1 and 0.050-0.50 ng/ml in plasma and 5-35 and 1-35 ng/ml in urine, respectively.
Conclusion:
The described highly selective and sensitive CP-I/CP-III LC-HRMS assay offers options for earlier characterization and clinical safety projections for OATP1B1/3-mediated drug-drug interactions along with pharmacokinetic analyses of a new chemical entity as part of first-in-human clinical studies.
