Targeted metabolomic analysis of 33 amino acids and biogenic amines in human urine by ion-pairing HPLC-MS/MS:biomarkers for tacrolimus nephrotoxicity after renal transplantation
Background:Calcineurin inhibitors(CNIs)nephrotoxicity especially for the widely applicable tacrolimus has become a major concern in post-transplant immunosuppression.Multi-parametric amino acid metabolomics is instrumental for biomarker identification of tacrolimus(Tac)nephrotoxicity,for which specific quantitative methods is highlighted as a premise.Methods:This article presented a targeted metabolomic assay to quantify 33 amino acids and biogenic amines in human urine by high performance liquid chromatography coupled with tandem mass spectrometry(HPLC-MS/MS).Chromatographic separation was carried out on an Agilent Zorbax SB-C18 column(3.0 mm×150 mm,5 μm)with addition of an ion-pairing agent in the mobile phase,and MS/MS detection was achieved in both the positive and negative multiple reaction monitoring(MRM)mode.Results:Good correlation coefficients(r2>0.98)were obtained for most analytes.Intra-and inter-day precision,stability,carryover and incurred sample reanalysis met with the acceptance criteria of the FDA Guidance(2001).Analysis on urine from healthy volunteers and renal transplantation patients with Tac nephrotoxicity confirmed symmetric dimethylarginine(SDMA)and serine(Ser)as biomarker at kidney injury,with AUC values of 0.95 and 0.81 in ROC analysis,respectively.Additionally,SDMA exhibited a tight correlation with serum creatinine,and was therefore indicative of renal function.Conclusions:The targeted metabolomic assay was time and cost prohibitive for amino acid analysis in human urine,facilitating the biomarker identification of Tac nephrotoxicity.
Urine Amino acid HPLC-MS/MS Tacrolimus Nephrotoxicity Transplantation Metabolomics
Tianyi Xia Shangxi Fu Qinghua Wang Yan Wen Shen-an Chan Sang Zhu Shouhong Gao Xia Tao Feng Zhang Wansheng Chen
Department of Pharmacy,Changzheng Hospital,Second Military Medical University,Shanghai 200003,P.R.Ch Department of Organ Transplantation,Changzheng Hospital,Second Military Medical University,Shanghai Department of Pharmacy,Xinqiao Hospital,Third Military Medical University,Chongqing 400037,P.R.China Agilent Technology,Shanghai 200080,P.R.China
国内会议
杭州
英文
3-14
2018-07-03（万方平台首次上网日期，不代表论文的发表时间）