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KMID : 1038020230310030139
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Translational and Clinical Pharmacology
2023 Volume.31 No. 3 p.139 ~ p.147
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Quantification of OATP1B1 endogenous metabolites coproporphyrin I and III in human urine
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Jang Yeon-Seo
Kang Ji-Hyun
Hwang Se-Jung
Chung Jae-Yong
Cho Joo-Youn
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Abstract
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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 15N4 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 (R2) 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 pre-study 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.
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KEYWORD
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Organic Anion-Transporting Polypeptides, Coproporphyrin I, Coproporphyrin III, Liquid Chromatography
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