An emerging analytical tool for highly sensitive quantitative analysis based on liquid chromatography-multiple-reaction monitoring cubed (MRM3) / 中国药科大学学报

@#Liquid chromatography-multiple-reaction monitoring (LC-MRM) has been widely recognized as the golden standard for multiple components-targeted quantitative analysis of complicated matrices,with extensive applications for analysis in such fields as chemical drugs, traditional Chinese medicines and foods.Unfortunately, when facing the task of quantitatively analyzing trace chemical components in complex matrices, MRM suffers dramatically from the background noise or matrix interference, leading to undesirable sensitivity and selectivity in terms of the lower limits of quantification (LOQ) and detection (LOD).In recent years, MRM cubed (MRM3), also known as MS3 scan, has received much attention because of its unique ability to significantly improve detection selectivity and sensitivity attributing to the successive ion filtering function, enabling LC-MRM3 as an emerging analytical tool.In this review,our attention is devoted to: 1) the illustration of the principle for MRM3; 2) parameter settings; and 3) the application progress of LC-MRM3 in such fields as the pursuit of biomarkers, pharmaceutical analysis, forensic analysis, toxicological analysis, food chemistry, and environmental analysis, aiming to provide a promising analytical tool of LC-MRM3 advantageous in the quantification analysis of trace chemical components in complex matrices.

Neuroprotective effects of Longxue Tongluo Capsule on ischemic stroke rats revealed by LC-MS/MS-based metabolomics approach / 中草药·英文版

OBJECTIVE@#The present study aimed to evaluate the therapeutic effect and explore the underlying mechanisms of Longxue Tongluo Capsule (LTC) on ischemic stroke rats.@*METHODS@#Twenty-six rats were randomly divided into four groups, including sham group, sham + LTC group, MCAO group, and MCAO + LTC group. Ischemic stroke rats were simulated by middle cerebral artery occlusion (MCAO), and LTC treatment group were orally administrated with 300 mg/kg of LTC once daily for seven consecutive days. LTC therapy was validated in terms of neurobehavioral abnormality evaluation, cerebral infarct area, and histological assessments. The plasma metabolome comparisons amongst different groups were conducted by UHPLC-Q Exactive MS in combination with subsequent multivariate statistical analysis, aiming to finding the molecules in respond to the surgery or LTC treatment.@*RESULTS@#Intragastric administration of LTC significantly decreased not only the neurobehavioral abnormality scores but also the cerebral infarct area of MCAO rats. The interstitial edema, atrophy, and pyknosis of glial and neuronal cells occurred in the infarcted area, core area, and marginal area of cerebral cortex were improved after LTC treatment. A total of 13 potential biomarkers were observed, and Youden index of 11 biomarkers such as LysoPC, SM, and PE were more than 0.7, which were involved in neuroprotective process. The correlation and pathway analysis showed that LTC was beneficial to ischemic stroke rats via regulating glycerophospholipid and sphingolipid metabolism, together with nicotinate and nicotinamide metabolism. Heatmap and ternary analysis indicated the synergistic effect of carbohydrates and lipids may be induced by flavonoid intake from LTC.@*CONCLUSION@#The present study could provide evidence that metabolomics, as systematic approach, revealed its capacity to evaluate the holistic efficacy of TCM, and investigate the molecular mechanism underlying the clinical treatment of LTC on ischemic stroke.

Authentic compound-free strategy for simultaneous determination of primary coumarins in Peucedani Radix using offline high performance liquid chromatography-nuclear magnetic resonance spectroscopy-tandem mass spectrometry

Herein, a strategy is proposed for the simultaneous determination of primary coumarins in Peucedani Radix (Chinese name: Qianhu). The methodology consists of three consecutive steps: 1) Semi-preparative LC in combination with a home-made automated fraction collection module to fragment the universal metabolome standard into ten fractions (Frs. I-X); 2) LC-accurate MS/MS and quantitative H NMR spectroscopy conducted in parallel to acquire the qualitative and quantitative data of each fraction; 3) Robust identification and quantification of components by use of LC coupled to multiple reaction monitoring. In this final step, the most significant fractions (Frs. III-X) were pooled to serve as the pseudo-mixed standard solution. Meticulous online parameter optimization was performed to obtain the optimal parameters, including ion transitions and collision energies. Concerns were particularly paid onto pursuing the parameters being capable of monitoring -specific isomers, notably praeruptorin E 3'-isovaleryl-4'-angeloylkhellactone. The quantitative performance of the method was validated according to diverse assays. Eleven primary coumarins (-) were unambiguously identified and absolutely quantified, even though no external reference compound was used. Above all, the integrated strategy not only provides a feasible pipeline for the quality assessment of Peucedani Radix, but more importantly, shows the potential for authentic compound-free quantitative evaluation of traditional Chinese medicines.

Application ofH NMR-based metabolomics for discrimination of different parts and development of a new processing workflow for

(CD) is one of the two authoritative source plants of Cistanches Herba, a well-known medicinal plant. Herein,H NMR spectroscopy was employed to characterize the chemical profile and to distinguish the different parts, as well as to propose a new processing workflow for CD. Signal assignment was achieved by multiple one and two dimensional NMR spectroscopic techniques in combination with available databases and authentic compounds. The upper parts of the plant were distinguished from the lower parts by combiningH NMR spectroscopic dataset with multivariate statistical analysis. A new processing method that hyphenated steaming with freeze-drying, was demonstrated to be superior to either steaming coupled with oven-drying or direct freeze-dryingholisticH NMR-based metabolomic characterization. Phenylethanoid glycosides, mainly echinacoside and acteoside, were screened out and confirmed as the chemical markers responsible for exhibiting the superiority of the new processing workflow, whereas serial primary metabolites, especially carbohydrates and tricarboxylic acid cycle metabolites, were found as the primary molecules governing the discrimination between the upper and lower parts of the plant. Collectively,H NMR spectroscopy was demonstrated as a versatile analytical tool to characterize the chemical profile and to guide the in-depth exploitation of CD by providing comprehensive qualitative and quantitative information.

Chemical constituents from n-butanol extract of aerial part of Polygala sibirica / 中国中药杂志

Nine compounds were isolated from the n-butanol extract of the aerial parts of Polygala sibirica by various column chromatographic methods. Their structures were identified by MS and NMR spectroscopic data as sibiricaxanthone F (1), amentoflavone (2), linarin (3), zigu-glucoside I (4), 3, 6'-disinapoyl sucrose (5), tenuifoliside A (6), 2, 4, 4-trimethyl-3-formyl-6-hy-droxy-2, 5-cyclohexadien-1-one (7), lanierone (8), and aralia cerebroside (9) , respectively. Compounds 2, 3, 4, 7, 8 were isolated from the genus Ploygala for the first time, and compound 9 was firstly isolated from the title plant.

Studies on chemical constituents of leaves of Aquilaria sinensis / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the chemical constituents of the leaves of Aquilaria sinensis, and provide a certain of basis for the comprehensive uses of the plant of A. sinensis.</p><p><b>METHOD</b>The chemical constituents were isolated by various column chromatographic method. The structures were identified by spectral analyses of NMR, MS, et al.</p><p><b>RESULT</b>Thirteen compounds were isolated and identified as 7-hyroxy-5, 4'-dimethoxy flovone (1), 5-hydroxy-7, 4'-dimethoxy flavone (2), luteolin-7-3',4'-trimethyl (3), isocorydine (4), 4-hydroxybenzoic acid (5), triacontenoic (6), hentriacontane (7), alpha-stigmasterol (8), epifriedelanol (9), friedelan (10), friedelin (11), genkwanin (12), 5, 4'-dihyroxy-7, 3'-dimethoxy flovone (13).</p><p><b>CONCLUSION</b>Compound 4 was obtained from this genus for the first time, compounds 1, 6-11, 13 were obtained from this species for the first time.</p>

Studies on xanthones from aerial parts of Polygala sibirica / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the chemical constituents of the aerial parts of Polygala sibirica systematically.</p><p><b>METHODS</b>The chemical constituents were isolated by various column chromatographic methods. The structures were identified by spectral data.</p><p><b>RESULT</b>Ten compounds were isolated and identified as 6-hydroxy-1, 2, 3, 7-tetramethoxy xanthone (1); 1, 2, 3, 6, 7-heptamethoxy xanthone (2); 1, 7-didydroxy-2, 3-methylenedioxy xanthone (3); 1, 7-dihydroxy-2, 3-dimethoxy xanthone (4); 1, 3, 7-trihydroxy-2-methoxy xanthone (5); 1, 6, 7-trihydroxy-2, 3-dimethoxy xanthone (6); alpha-spinasterol (7); alpha-spinasterolic-3-O-beta-D-glucoside (8); squalene (9) and polygital (10).</p><p><b>CONCLUSION</b>Compounds 1-10 were isolated from this species for the first time.</p>