期刊
BIOANALYSIS
卷 10, 期 9, 页码 673-689出版社
FUTURE SCI LTD
DOI: 10.4155/bio-2017-0272
关键词
drug-drug interactions; endogenous biomarkers; HILIC-MS/MS; N-1-methylnicotinamide; renal transporters
Aim: N-1-methylnicotinamide (1-NMN) has been proposed as a potential clinical biomarker to assess drugdrug interactions involving organic cation transporters (OCT2) and multidrug and toxin extrusion protein transporters. Results: A hydrophilic interaction liquid chromatography-MS/MS assay, to quantify 1-NMN, in human plasma and urine is reported. Materials & methods: A hydrophilic interaction chromatography (HILIC)-tandem mass spectrometry (MS/MS) assay to quantify 1-NMN in human plasma and urine is reported. The basal 1-NMN levels in plasma and urine were 4-120 and 2000-15,000 ng/ml, respectively. Conclusion: 1-NMN plasma AUCs increased two- to fourfold versus placebo following the administration of a clinical candidate that in vitro experiments indicated was an OCT2 inhibitor. The described hydrophilic interaction liquid chromatography-MS/MS assay can be used to assess a clinical compound candidate for the inhibition of OCT2 and multidrug and toxin extrusion protein transporter in first-in-human studies.
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