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Objective To detect whether patients with gastric cancer had unique serum metabolomic characteristics by liquid chromatography-mass spectrometry (LC-MS) metabolomic analysis,and to screen potential markers for early gastric cancer and to preliminarily explore the related metabolic pathways.Methods At the First Affiliated Hospital of Soochow University,66 patients with gastric cancer and 44 patients with benign gastric disease from July,2017 to January,2018 were enrolled,and 50 healthy subjects served as controls.Twenty-five patients with gastric cancer at stage Ⅰ and Ⅱ and 25 patients with gastric cancer at stage Ⅲ and Ⅳ were selected from the 66 patients with gastric cancer,and 25 subjects were also selected from 50 healthy controls.The plasma small molecule metabolites of patients with gastric cancer and benign gastric disease and healthy controls were detected by LC-MS method.Multivariate logistic regression analysis was used to establish and validate the principal component analysis (PCA) model and partial least squares-discriminant analysis (PLS-DA) model and screen the differential metabolites.The receiver operating characteristic curve analysis was used to evaluated the clinical efficacy of differential metabolites.Results PCA and PLS-DA models showed that gastric cancer had a obviously specific metabolites profile,the profile of benign gastric disease overlapped with that of gastric cancer and healthy controls.The results of multivariate logistic regression analysis confirmed that four metabolites including isoleucine,benzophenone,sphingosine-1-phosphate and galactopyranose set could be used to establish an optimal diagnostic model.The area under the curve (AUC)(95％ confidence interval (CI)) was 0.963 (0.930 to 0.997),and the best cut off value,sensitivity and specificity were 0.871,93.1％ and 94.0％,respectively.Meanwhile,patients with gastric cancer at stage Ⅰ + Ⅱ and stage Ⅲ + Ⅳ had a distinct clustering trend compared with the control group.In the serum of patients with gastric cancer at stage Ⅰ + Ⅱ and stage Ⅲ + Ⅳ,a total of 24 differential metabolites were identified,theconcentration of five of which including lysine,carnitine,benzenesulfonamide,arginine and docosahexaenoic acid ethyl ester,increased along with the progression of gastric cancer.Pipecolic acid and kynurenine might served as biomarkers for early and mid gastric cancer (stage [+ Ⅱ) screening.Conclusions LC-MS metabolomic effectively confirm the unique changes of serum metabolites in patients with gastric cancer.The screened differential metabolites have potential clinical application value for predicting the risk of gastric cancer.
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Curcumin is a widely studied natural compound which has shown tremendous in vitro therapeutic potential. Despite that, the clinical efficacy of the native curcumin is weak due to its low bioavailability and high metabolism in the gastrointestinal tract. During the last decade, researchers have come up with different formulations with a focus on improving the bioavailability of curcumin. As a result, a significant number of bioavailable curcumin-based formulations were introduced with the varying range of enhanced bioavailability. The purpose of this review is to collate the published clinical studies of curcumin products with improved bioavailability over conventional (unformulated) curcumin. Based on the literature search, 11 curcumin formulations with available human bioavailability and pharmacokinetics data were included in this review. Further, the data on clinical study design, analytical method, pharmacokinetic parameters and other relevant details of each formulation were extracted. Based on a review of these studies, it is evident that better bioavailability of formulated curcumin products is mostly attributed to improved solubility, stability, and possibly low first-pass metabolism. The review hopes to provide a quick reference guide for anyone looking information on these bioavailable curcumin formulations. Based on the published reports, NovaSol® (185), CurcuWin® (136) and LongVida® (100) exhibited over 100-fold higher bioavailability relative to reference unformulated curcumin. Suggested mechanisms accounting for improved bioavailability of the formulations and details on the bioanalysis methods are also discussed.
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The objective of current study was to develop a validated specific stability indicating reversed-phase liquid chromatographic method for the quantitative determination of desvenlafaxine in bulk sample and pharmaceutical dosage form in the presence of degradation products.Forced degradation studies were performed on bulk sample of desvenlafaxine as per ICH prescribed stress conditions using acid,base,oxidative and photolytic degradation to show the stability indicating power of the method.Significant degradation was observed under acidic stress condition and the degradation product formed was identified by LC-MS and a degradation pathway for drug has been proposed.Successful separation of drug from degradation products formed under stress conditions was achieved on a SymmetryShield column C18 (5 μm,250 mm × 4.6 mm,i.d.) using the mobile phase consisting of a mixture of 0.2％ (v/v) triethylamine in ammonium acetate (0.05 M; pH 6.5) and methanol using isocratic gradient.