AI Article Synopsis
- The study investigates the use of coproporphyrin-I (CP-I) and coproporphyrin-III (CP-III) as potential biomarkers for evaluating drug-drug interactions involving specific hepatic transporters (OATP1B1 and OATP1B3).
- Using a TripleTOF API6600 mass spectrometer, researchers found that doubly charged ions of CP-I/CP-III showed improved sensitivity and selectivity in plasma and urine analysis compared to singly charged ions.
- The sensitive LC-HRMS assay developed can help in the early identification of drug interactions and enhance clinical safety assessments during first-in-human trials.
Article Abstract
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.
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| http://dx.doi.org/10.4155/bio-2017-0181 | DOI Listing |
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