Quantitative analysis of biomarkers of liver and kidney injury in serum and urine using ultra-fast liquid chromatography with tandem mass spectrometry coupled with a hydrophilic interaction chromatography column: Application to monitor injury induced by E

Abstract

Fast and sensitive monitoring of drug-induced liver and kidney injury in early stage is beneficial. An ultrafast liquid chromatography with tandem mass spectrometry assay was developed and validated to simultaneously determine ten endogenous biomarkers in serum and urine, including hippuric acid, phenylacetylglycine, 5-oxoproline, cholic acid, taurine, indoleacetic acid, 3-indoxyl sulfate, guanidinosuccinic acid, guanidinoacetic acid and uric acid. A CAPCELL CORE PC column (2.1 × 150 mm, 2.7 μm) was adopted for analytes separation. Gradient elution was performed with acetonitrile and water containing 5 mM ammonium acetate. Simple protein precipitation was applied in sample preparation. Good linearities were achieved with all the regression coefficients above 0.9911. Accuracy was 2.9-14.2% in serum and 4.1-14.6% in urine. The mean recovery was above 70% with acceptable matrix effects. The method was applied to monitor injury induced by Euphorbiae pekinensis Radix with a subacute rats model. All the biomarkers showed obvious concentration changes during the injury period. Furthermore, several biomarkers showed significant changes in earlier stage when compared with the current clinical serum bio-parameters. The method might be helpful for early diagnosis of drug induced liver and kidney injury in clinical after tested on more drugs.

Serial-omics characterization of equine urine

“…From the untargeted experiment, hippuric acid, a common carboxylic acid found in the urine of horses and other plant eating species was the most abundant molecule identified followed by creatinine, a breakdown product of creatine that is commonly secreted through urine and is used to monitor normal kidney function and can be used as a urine control metabolite for normalization [ 50 ]. Phenylacetylglycine was also very abundant and is a gut microbial co-metabolite with hippuric acid and well-studied using LC-MS/MS methods from urine as phospholipidosis markers [ 51 , 52 ]. p-Cresol glucuronide is another common urine metabolite derived from intestinal bacteria.…”

LC-MS-based metabolomics analysis to identify meprin-β-associated changes in kidney tissue from mice with STZ-induced type 1 diabetes and diabetic kidney injury

“…Hippuric acid is a product of amino acid metabolism by gut microbiota and has been shown to be part of metabolite panels that change in kidney injury. Urinary levels of hippuric acid have also been shown to significantly increase in acute kidney injury (85).…”

Metabonomics analysis of kidneys in rats administered with chronic low‐dose cadmium by ultra‐performance liquid chromatography‐mass spectrometry

“…The accumulation of GSA and other toxic guanidine-based compounds has been reported to cause kidney dysfunction (Levillain, Marescau, Possemiers, Banchaabouchi, & De Deyn, 2001). Guanidine-based compounds were detected in patients with chronic renal failure by high-performance liquid chromatography, and the results showed that GSA levels were significantly elevated in the body, suggesting that GSA may be used as a biomarker of kidney damage (Tanaka, Takahashi, Mizokuchi, Shimada, & Koide, 1999;Zhang, Gu, Jiang, Bi, & Chen, 2016). GSA is produced from the oxidation of argininosuccinic acid (an amino acid) by free radicals (Perez, Epstein, Rietberg, & Loutzenhiser, 1978;Schepers et al, 2010).…”