Quantification of OATP1B1 endogenous metabolites coproporphyrin I and III in human urine
- Author:
Yeonseo JANG
1
;
Jihyun KANG
;
Sejung HWANG
;
Jae-Yong CHUNG
;
Joo-Youn CHO
Author Information
- Publication Type:Original Article
- From:Translational and Clinical Pharmacology 2023;31(3):139-147
- CountryRepublic of Korea
- Language:English
- Abstract: Coproporphyrin (CP)-I and CP-III are the markers of organic anion-transporting polypeptides’ (OATPs) activities, and they are porphyrin metabolites that originate from heme synthesis.Furthermore, CP-I and CP-III, which are OATP1B endogenous metabolites, have gradually attracted the attention of scientists and researchers in recent years. Previous studies have also observed CP-I and CP-III levels as clinical biomarkers for predicting OATP1B inhibition in drug–drug interaction studies. To establish an accurate ultra-high performance liquid chromatography–mass spectrometry method for the quantitation of CP-I and CP-III, we reviewed previous methodological publications and applied them to a clinical pharmacology study using a human urine matrix. We used 13.25 M formic acid as a working solution for internal standards (CP-I 15 N 4 and CP-III d8 ) to avoid isobaric interference. The calibration curve showed good linearity in the range of 1–100 ng/mL, with a correlation coefficient (R 2 ) higher than 0.996 in each validation batch. Both the between-run and within-run assays achieved good precision and accuracy, and we found that both CP-I and CP-III were stable in the prestudy validation. The method exhibited suitable dilution integrity, allowing for the re-analysis of samples with concentrations exceeding the upper limit of quantification through dilution.Overall, the application of the described method in a clinical study revealed that it can be utilized effectively to monitor drug–drug interactions mediated by OATP1B.
