Dataset Information

Development and validation of an UHPLC-Orbitrap-HRMS method for rapid determination of endogenous L-carnitine in patients on hemodialysis/peritoneal dialysis and its application to promote rational drug use.

ABSTRACT:

Background

L-carnitine is an endogenous vitamin-like amino acid derivate which plays an essential role in energy metabolism and can be easily lost via dialysis. Deficiency of L-carnitine has great effects on many aspects of bodily functions. To determine the deficiency degree and adjust the supplementation dose, a rapid, sensitive, and specific method for the detection of endogenous L-carnitine in the plasma of dialysis patients using ultra-high performance liquid chromatography-Orbitrap high resolution mass spectrometry (UHPLC-Orbitrap-HRMS) was developed and validated.

Methods

The plasma samples were processed by protein precipitation and centrifugation before analysis using UHPLC-Orbitrap-HRMS. Sample separation was achieved with a hydrophilic interaction liquid chromatography (HILIC) column, using an isocratic elution with a runtime of 5 min. The separated analytes were detected by positive ionization mode in full scan mode and targeted-single ion monitoring (t-SIM) mode. Mildronate was used as the internal standard (IS).

Results

All the plasma could be detected in the range of 6.169 to 197.394 µM, with adequate accuracy, precision, and recovery. The method was validated in fortified validation with relative standard deviations (RSD) 5.15-8.74%. This method was applied to the analysis of 105 dialysis patients and 39 healthy participants, the results revealed that peritoneal dialysis patients without L-carnitine supplementation should pay more attention to L-carnitine monitoring, meanwhile, all the hemodialysis patients were advised to be routinely given a full dose of L-carnitine, no matter whether they had taken L-carnitine or not.

Conclusions

This study developed a simple and rapid UHPLC-Orbitrap-HRMS method for detection of endogenous L-carnitine in dialysis patients, which could be useful to promote rational drug use.

SUBMITTER: Jiang WT

PROVIDER: S-EPMC8848361 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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Publications

Development and validation of an UHPLC-Orbitrap-HRMS method for rapid determination of endogenous L-carnitine in patients on hemodialysis/peritoneal dialysis and its application to promote rational drug use.

Jiang Wen-Ting WT Tang Liu-Xing LX Pan Jie J Su Cun-Jin CJ Shen Zhu Z Hu Zhan-Hong ZH Zhan Zhou-Bing ZB Shi Ai-Ming AM

Annals of translational medicine 20220101 2

<h4>Background</h4>L-carnitine is an endogenous vitamin-like amino acid derivate which plays an essential role in energy metabolism and can be easily lost via dialysis. Deficiency of L-carnitine has great effects on many aspects of bodily functions. To determine the deficiency degree and adjust the supplementation dose, a rapid, sensitive, and specific method for the detection of endogenous L-carnitine in the plasma of dialysis patients using ultra-high performance liquid chromatography-Orbitrap ...[more]

PMID: 35282068

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Project description:BackgroundVascular calcification is seen in most patients on dialysis and is strongly associated with cardiovascular mortality. Vascular calcification is promoted by phosphate, which generally reaches higher levels in hemodialysis than in peritoneal dialysis. However, whether vascular calcification develops less in peritoneal dialysis than in hemodialysis is currently unknown. Therefore, we compared coronary artery calcification (CAC), its progression, and calcification biomarkers between patients on hemodialysis and peritoneal dialysis.MethodsWe measured CAC in 134 patients who had been treated exclusively with hemodialysis (n = 94) or peritoneal dialysis (n = 40) and were transplantation candidates. In 57 of them (34 on hemodialysis and 23 on peritoneal dialysis), we also measured CAC progression annually up to 3 years and the inactive species of desphospho-uncarboxylated matrix Gla protein (dp-ucMGP), fetuin-A, osteoprotegerin. We compared CAC cross-sectionally with Tobit regression. CAC progression was compared in 2 ways: with linear mixed models as the difference in square root transformed volume score per year (ΔCAC SQRV) and with Tobit mixed models. We adjusted for potential confounders.ResultsIn the cross-sectional cohort, CAC volume scores were 92 mm3 in hemodialysis and 492 mm3 in peritoneal dialysis (adjusted difference 436 mm3; 95% CI -47 to 919; p = 0.08). In the longitudinal cohort, peritoneal dialysis was associated with significantly more CAC progression defined as ΔCAC SQRV (adjusted difference 1.20; 95% CI 0.09 to 2.31; p = 0.03), but not with Tobit mixed models (adjusted difference in CAC score increase per year 106 mm3; 95% CI -140 to 352; p = 0.40). Peritoneal dialysis was associated with higher osteoprotegerin (adjusted p = 0.02) but not with dp-ucMGP or fetuin-A.ConclusionsPeritoneal dialysis is not associated with less CAC or CAC progression than hemodialysis, and perhaps with even more progression. This indicates that vascular calcification does not develop less in peritoneal dialysis than in hemodialysis.

Project description:The incidence of cerebral ischemic stroke characterized by high mortality is increasing every year. Danshen Chuanxiongqin Injection (DSCXQ), a traditional Chinese medicine (TCM) preparation, is often applied to treat cerebral apoplexy and its related sequelae. However, there is a lack of systematic research on how DSCXQ mediates its protective effects against cerebral ischemia stroke. Metabolomic analysis based on UHPLC-Q-Orbitrap HRMS was employed to explore the potential mechanisms of DSCXQ on ischemic stroke induced by transient middle cerebral artery occlusion (MCAO). Pattern analysis and metabolomic profiling, combined by multivariate analysis disclosed that 55 differential metabolites were identified between Sham group and Model group, involving sphingolipid metabolism, glycerophospholipid metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, primary bile acid biosynthesis, pantothenate and CoA synthesis and valine, leucine and isoleucine biosynthesis pathways. DSCXQ could reverse brain metabolic deviations in stroke by significantly upregulating the levels of L-tryptophan, Lyso (18:0/0:0), LPC (18:2), Indole-3-methyl acetate, and downregulating the levels of sphinganine 1-phosphate, L-threonic acid, glutaconic acid and N6,N6,N6-Trimethyl-L-lysine. In our study, we focused on the neuroprotective effects of DSCXQ against neuroinflammatory responses and neuronal apoptosis on a stroke model based on sphingolipid metabolism. The expressions of Sphk1, S1PR1, CD62P, Bcl-2, Bax, and cleaved Caspase-3 in brain tissue were evaluated. The neurological deficit, cerebral infarct size and behavioral abnormality were estimated. Results showed that DSCXQ intervention significantly reduced cerebral infarct size, ameliorated behavioral abnormality, inhibited the expression of Sphk1, S1PR1, CD62P, Bax, Cleaved Caspase-3, while increased the level of Bcl-2, and prevented neuronal apoptosis. The limitations are that our study mainly focused on the verification of sphingolipid metabolism pathway in stroke, and while other metabolic pathways left unverified. Our study indicates that SphK1-SIP axis may potentiate neuroinflammatory responses and mediate brain damage through neuronal apoptosis, and DSCXQ could suppress the activity of SphK1-SIP axis to protect brain tissue in cerebral ischemia. In conclusion, this study facilitates our understanding of metabolic changes in ischemia stroke and the underlying mechanisms related to the clinical application of DSCXQ.

Dataset Information

Development and validation of an UHPLC-Orbitrap-HRMS method for rapid determination of endogenous L-carnitine in patients on hemodialysis/peritoneal dialysis and its application to promote rational drug use.

Background

Methods

Results

Conclusions

Publications

Development and validation of an UHPLC-Orbitrap-HRMS method for rapid determination of endogenous L-carnitine in patients on hemodialysis/peritoneal dialysis and its application to promote rational drug use.

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