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: 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.

Efficacy of proton pump inhibitors for patients with duodenal ulcers: A pairwise and network meta-analysis of randomized controlled trials.

BACKGROUND/AIM: To compare the efficacy and tolerance of different proton pump inhibitors (PPIs) in different doses for patients with duodenal ulcers. MATERIALS AND METHODS: An electronic database was searched to collect all randomized clinical trials (RCTs), and a pairwise and network meta-analysis were performed. RESULTS: A total of 24 RCTs involving 6188 patients were included. The network meta-analysis showed that there were no significant differences for the 4-week healing rate of duodenal ulcer treated with different PPI regimens except pantoprazle 40 mg/d versus lansoprazole 15 mg/d [Relative risk (RR) = 3.57; 95% confidence interval (CI) = 1.36-10.31)] and lansoprazole 30 mg/d versus lansoprazole 15 mg/d (RR = 2.45; 95% CI = 1.01-6.14). In comparison with H2receptor antagonists (H2RA), pantoprazole 40 mg/d and lansoprazole 30 mg/d significantly increase the healing rate (RR = 2.96; 95% CI = 1.78-5.14 and RR = 2.04; 95% CI = 1.13-3.53, respectively). There was no significant difference for the rate of adverse events between different regimens, including H2RA for a duration of 4-week of follow up. CONCLUSION: There was no significant difference for the efficacy and tolerance between the ordinary doses of different PPIs with the exception of lansoprazle 15 mg/d.

Norcantharidin-associated galactosylated chitosan nanoparticles for hepatocyte-targeted delivery.

In this study a new chitosan (CS) derivative, galactosylated chitosan (GC), was synthesized and used to prepare norcantharidin-associated GC nanoparticles (NCTD-GC NPs) by taking advantage of the ionic cross-linkage between the molecules of the anti-hepatocarcinoma medicine NCTD and of the GC as carrier. NCTD-GC NPs were obtained with average particle size of 118.68 +/- 3.37 nm, entrapment efficiency of 57.92 +/- 0.40%, and drug-loading amount of 10.38 +/- 0.06%. Several important factors influencing the entrapment efficiency, drug-loading amount, and particle size of NCTD-GC NPs were studied. The characteristics of sustained and pH-sensitive release of NCTD from NCTD-GC NPs in vitro were studied. In addition, in vitro cellular uptake and cytotoxicity of nanoparticles to hepatoma cell lines SMMC-7721 and HepG2 were also investigated. In vitro, and compared to CS-based NCTD-CS NPs, NCTD-GC NPs demonstrated satisfactory compatibility with hepatoma cells and strong cytotoxicity against hepatocellular carcinoma cells. In vivo antitumor activity of NCTD-GC NPs was evaluated in mice bearing H22 liver tumors. NCTD-GC NPs displayed tumor inhibition effect in mice, better than either the free NCTD or the NCTD-CS NPs. As a hepatocyte-targeting carrier, GC NPs are potentially promising for clinical applications. FROM THE CLINICAL EDITOR: In this paper, a galactosylated chitosan (GC), was synthesized and norcantharidin (NCTD)-associated galactosylated chitosan nanoparticles (NCTDGC NPs) were generated by coupling NCTD--an anti-hepatocarcinoma drug--and GC as carrier. Compared to chitosan nanoparticles, NCTD-GC-NPs demonstrated satisfactory compatibility with hepatoma cells and strong cytotoxicity against the cells.