Highly sensitive simultaneous quantification of indoxyl sulfate and 3‐carboxy‐4‐methyl‐5‐propyl‐2‐furanpropanoic acid in human plasma using ultra‐high‐performance liquid chromatography coupled with tandem mass spectrometry

Abstract

Indoxyl sulfate and 3‐carboxy‐4‐methyl‐5‐propyl‐2‐furanpropanoic acid are uremic toxins that accumulate in renal failure and have been reported to decrease the activities of the drug‐metabolizing enzyme cytochrome P450 3A and the drug transporter organic anion transporting polypeptides 1B, respectively. In this study, we established and validated an assay for simultaneous quantification of indoxyl sulfate and 3‐carboxy‐4‐methyl‐5‐propyl‐2‐furanpropanoic acid in human plasma. The samples were pretreated by solid‐phase extraction, and measured by ultra‐high‐performance liquid chromatography–tandem mass spectrometry. The validation results for this assay were within the acceptable limits recommended by the US Food and Drug Administration, with a lower limit of quantitation of 0.05 μg/mL for both indoxyl sulfate and 3‐carboxy‐4‐methyl‐5‐propyl‐2‐furanpropanoic acid. Recovery rates of indoxyl sulfate and 3‐carboxy‐4‐methyl‐5‐propyl‐2‐furanpropanoic acid corrected by internal standard were 100.7–101.9 and 100.2–101.3%, respectively. Matrix effects of indoxyl sulfate and 3‐carboxy‐4‐methyl‐5‐propyl‐2‐furanpropanoic acid corrected by internal standard were 101.1–105.5 and 97.0–103.8%, respectively. The validated assay was used to analyze indoxyl sulfate and 3‐carboxy‐4‐methyl‐5‐propyl‐2‐furanpropanoic acid concentrations in the plasma samples of healthy volunteers and patients with chronic kidney disease. All the measured plasma indoxyl sulfate and 3‐carboxy‐4‐methyl‐5‐propyl‐2‐furanpropanoic acid concentrations were within the calibration ranges. This novel method may contribute to predicting the activities of drug‐metabolizing enzymes and drug transporters in individual patients.

Evaluation of effects of indoxyl sulfate and parathyroid hormone on CYP3A activity considering the influence of CYP3A5 gene polymorphisms

“…The within‐batch precision (% coefficient of variation) was below 9.9% for both 4β‐OHC and 4α‐OHC. Plasma indoxyl sulfate concentrations were quantified by our previous UHPLC–MS/MS method 25 . The LLOQ was 0.05 μg/mL for indoxyl sulfate.…”

“…Plasma indoxyl sulfate concentrations were quantified by our previous UHPLC-MS/MS method. 25 The LLOQ was 0.05 μg/mL for indoxyl sulfate. The within-batch accuracy was 92.5%-107.3%, and the within-batch precision was below 5.2%.…”

Gut-Derived Uremic Toxins in CKD: An Improved Approach for the Evaluation of Serum Indoxyl Sulfate in Clinical Practice

“…Conventionally, liquid chromatography–tandem mass spectrometry (LC-MS/MS) represents the main diagnostic system in the measurement of IS thanks to its elevated performance [ 28 , 29 , 30 , 31 ]. Nevertheless, it requires dedicated skills and costly equipment, and results are obtained after a long period.…”

Portable, Intelligent Fluorescence Sensing Platform for Dense Convolutional Network-Capable Detection of Indophenol Sulfate and Methylmalonic Acid Using a Luminescent Eu@HOF Film

“…Until now, common methods for monitoring IS and MMA have primarily included electrochemical, 12 high-performance liquid chromatography, 13 and liquid chromatography−mass spectrometry methods. 14 These methods require complex sample pretreatment processes, expensive instruments, and professional technical personnel, which greatly limits the application in on-site and real-time detection. Hence, developing a novel optical sensing platform with high portability and low cost, which can timely monitor IS and MMA, will be a great challenge in the future.…”

“…Methylmalonic acid (MMA) in urine is considered as a potential biomarker for the deficiency of vitamin B12, which is conducive to prevent and diagnose DPN. , Therefore, it is very important to design a high-sensitivity detector for early warning and prevention of CKD and DPN, which can detect IS in serum and MMA in urine. Until now, common methods for monitoring IS and MMA have primarily included electrochemical, high-performance liquid chromatography, and liquid chromatography–mass spectrometry methods . These methods require complex sample pretreatment processes, expensive instruments, and professional technical personnel, which greatly limits the application in on-site and real-time detection.…”