brakewindow9
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s.Drying method is one of the important factors affecting quality of traditional Chinese medicine. To study the effect of shaded drying and hot air drying on steroidal saponins of Paridis Rhizoma (PR), high performance liquid chromatography (HPLC) analysis was used to investigate the difference of Paris polyphylla var. chinensis (PPC) samples treated by different methods, and then, a rapid and reliable ultra-high performance liquid chromatography (UPLC) method was established to quantitatively analyze the content change of ten steroidal saponins. Hot air drying at 50 ℃ could obviously improve the content of polyphyllin Ⅶ, 17-hydroxygracillin and polyphyllin H, which were major steroidal saponins in PPC. Based on that, the main component changes induced by different drying methods were further analyzed using ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS), and the structural identification of varied components revealed that hot air drying could promote the transformation of proto-pennogenyl glycosides to pennogenyl glycosides. Selleck VU0463271 This phenomenon was also found in other plants of genus Paris rich in diosgenyl glycosides. The present study provided a useful method for improving quality of PR and valuable information for TCM containing steroidal saponins.Kinase inhibitors (KIs) and antiandrogen drugs (AAs) are oral anticancer drugs with narrow therapeutic index that exhibit high inter- and intra-individual variability. We describe here a UPLC-MS/MS method for the simultaneous quantification of nine KIs cobimetinib, dasatinib, ibrutinib, imatinib, nilotinib, palbociclib, ruxolitinib, sorafenib and vemurafenib; two active metabolites of them N-desmethyl imatinib, N-oxide sorafenib; and two AAs abiraterone and enzalutamide; with short pre-treatment and run time in order to be easily used in clinical practice for their therapeutic drug monitoring (TDM) and facilitating pharmacokinetics and pharmacokinetics/pharmacodynamics studies. Plasma samples were prepared by a single-step protein precipitation. Analytes were separated on a Waters Acquity UPLC® T3 HSS C18 column by non-linear gradient elution; with subsequent detection by Xevo® TQD triple quadrupole tandem mass spectrometer in a positive ionization mode. Analysis time was 2.8 min per run, and all analytes eluted within 1.46-1.97 minutes. The analytical performance of the method in terms of specificity, sensitivity, linearity, precision, accuracy, matrix effect, extraction recovery, limit of quantification, dilution integrity and stability of analytes under different conditions met all criteria for a bioanalytical method for the quantification of drugs. The calibration curves were linear over the range of 1-500 ng/mL for abiraterone, dasatinib and ibrutinib; 5-500 ng/mL for cobimetinib and palbociclib; 10-5,000 ng/mL for imatinib, N-desmethyl imatinib, nilotinib, sorafenib, N-oxide sorafenib and ruxolitinib; 100-50,000 ng/mL for enzalutamide and 100-100,000 ng/mL for vemurafenib with coefficient of correlation above 0.995 for all analytes. This novel method was successfully applied to TDM in clinical practice. Trisomy 21 is a serious chromosome abnormality. The conventional Down's screening test is the most widely used for trisomy 21 screening. However, this method could lead to a higher false positive rate. Therefore, we aim to analyze steroid profile in second-trimester pregnant women and identify novel serum biomarkers of trisomy 21. We employed an LC-MS/MS method to measure the steroid profile. The concentrations and product-to-substrate ratios in 71 second-trimester pregnant women were determined and statistically analyzed to identify novel biomarkers for trisomy 21 screening. We found that there were significant differences in levels of E3, 11-deoxycortisol, and 11-deoxycortisol /17-hydroxyprogesterone between two groups. The OPLS-DA plots revealed obvious separation between two groups. Combining VIP analysis (VIP > 1.0) with volcano plot (P < 0.05 and fold change >1.2 or < 0.83), 11-deoxycortisol was identified as a novel biomarker for trisomy 21. After controlling for confounders, we found 11-deoxycortisol was associated with trisomy 21 (adjusted P = 0.009), and the fully adjusted OR (95 % CI) was 0.098 (0.016-0.593) in highest quartile versus lowest quartile of 11-deoxycortisol (P = 0.011). Steroid profile analysis for the first time showed that steroid hormones perturbations occurred in pregnant women carrying a fetus affected by trisomy 21 and decreased 11-deoxycortisol levels were associated with trisomy 21.Steroid profile analysis for the first time showed that steroid hormones perturbations occurred in pregnant women carrying a fetus affected by trisomy 21 and decreased 11-deoxycortisol levels were associated with trisomy 21.Plant saponins are important natural product with biologically active. However, the metabolism of these compounds has rarely been studied due to their low bioavailability and the complexity of their metabolite structures. In this study, ultra-performance liquid chromatography/Fusion Lumos Orbitrap mass spectrometry was used to analyze the metabolites of hederasaponin B in vivo, and its possible metabolic pathways were proposed. After oral administration of the parent drug, a total of 47 metabolites are identified in rat feces (42), urine (11), and plasma (9) samples. These metabolites resulted from the metabolic processes in phases I and II reactions involved in deglycosylation, hydroxylation, acetylation, oxidation, gluconalciation and glycosylations. Deglycosylation is the main metabolic pathway (accounts for 52.46 % of all metabolites in feces samples). Among the identified metabolites, four were glycosylated (deprotonated precursors at m/z = 1335.7, 1365.7, 1467.9, and 1379.6) with higher molecular weight than the parent drug . These glycosylated compounds account for 11.55 % of the metabolites in rat feces according to the semi-quantitative chromatographic peak areas. To sum up, the results of this study provide a basis for further understanding the metabolism of plant saponins in vivo.

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