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Lipase inhibitors are an attractive class of hypolipidemic compounds, which inhibit the activity of human pancreatic lipase, thereby preventing the absorption of triglycerides in vivo. As a library of promising lead compounds for drug development, traditional Chinese medicine (TCM) has gained growing attention in quick discovery and identification of enzyme inhibitors of natural-origin. The purpose of this work was to discover unknown lipase inhibitors from Alisma orientale by the activity oriented analysis method thin-layer chromatography-bioautography, then use electrospray ionization mass spectrometry technology via the elution based TLC-MS interface to identify their structures. As a result, eleven natural lipase inhibitors from Alisma orientale extracts were identified based on molecular mass and fragment ions obtained by HPTLC-MS, and further confirmed by a series of complementary means including UV spectra, 1H NMR characteristic proton signals and polarity of compounds, eleven lipase inhibitors were tentatively assigned as triterpenoids alisol B (m/z 495.50 [M + Na]+), alisol B 23-acetate (m/z 537.58 [M + Na]+), 11-deoxy-alisol B (m/z 479.50 [M + Na]+), 11-deoxy-alisol B 23-acetate (m/z 521.50 [M + Na]+), alisol A/epialisol A (m/z 513.50 [M + Na]+), 16-oxo-11-deoxy-alisol A (m/z 511.50 [M + Na]+), 16-oxo-alisol A (527.50 [M + Na] +), alisol C (m/z 509.58 [M + Na]+), alisol C 23-acetate (m/z 551.50 [M + Na]+), alisol M 23-acetate (m/z 567.50 [M + Na]+), and alismanol Q/neoalisol (m/z 493.42 [M + Na]+). The integrated approach is an efficient method for rapid screening lipase inhibitors from complex plant extracts and provides a reasonable and favorable basis for the identification and separation of other enzymatic system and other important compounds with therapeutic values.The complexity of Tobradex® ointment formulation (dexamethasone 0.1 wt% and tobramycin 0.3 wt%) and the high cost of pharmacokinetic (PK) studies in human aqueous humor may prevent generic drug companies from moving forward with a Tobradex®-equivalent product development. The in vitro drug release test would be an alternative approach for differentiating the generic formulations containing both dexamethasone (DEX) and tobramycin (TOB), and the results should be correlated with the in vivo ocular PK studies for further evaluation. To facilitate the in vivo ocular PK studies, a sensitive, rapid and specific liquid chromatography-tandem mass spectrometry (LC-MS/MS) method that can simultaneously quantify both DEX and TOB in rabbit ocular matrices including tear, aqueous humor and cornea was established and validated. The lower limit of quantification (LLOQ) was 1.5 ng/ml for DEX and 3 ng/ml for TOB with good precision and accuracy. Both intra- and inter-batch precisions were within ±15%, and the accuracy for all QCs was within the range of 85-115%. This new method was successfully applied for a pilot pharmacokinetic analysis of DEX and TOB in rabbit tears after topical administration of Tobradex® ointment.A chemometric evaluation of the information provided by different color scale fingerprints in thin layer chromatographic analysis of complex samples is proposed for the correct classification of a set of medicinal plant extracts. The fingerprints of the samples were acquired on HPTLC Silica gel 60 F254 and HPTLC Silica gel 60 plates using multiple levels of visualization under UV light. Images processing on red (R), green (G), blue (B) and respectively grey (K) color scale selection was used in order to evaluate the complete chromatographic profile of the extracts. Combination of Principal Component Analysis (PCA) and Factor Analysis (FA) method was applied in order to reveal the individual contribution of each color scales in the analysis of chromatographic fingerprints. The suggested technique provides an applicable strategy to screen for efficacy-associated color scale for grouping/classification of the extracts exploiting the information provided by HPTLC fingerprints. The principal component analysis and linear discriminant analysis (PCA-LDA) method was applied for the evaluation of numerical data provided by color scale fingerprints digitization and for samples classification. A correct classification of the analyzed extracts according to the plants phylum was revealed by color scale fingerprints analysis. The proposed methodology could be considered as a promising tool with future applications in plant material investigations even from the taxonomic perspective classification.In this study, polyamide and MCI GEL® CHP20P were employed as stationary phases in medium pressure chromatography (MPC) for the efficient preparative separation of bergenin from Saxifraga atrata. Ethanol-water, methanol-water, and acetonitrile-water mobile phases all showed good enrichment capacity for bergenin fraction when polyamide was used as a stationary phase. After 5 cycles of polyamide MPC using acetonitrile/water, 1.2 g of bergenin fraction was isolated from 180 g Saxifraga atrata herb. AZD9291 clinical trial Further purification of this fraction was conducted using MCI GEL® CHP20P styrene-divinylbenzene beads. The bergenin fraction was separated into two fractions, and after three runs of MPC, 714.2 mg of bergenin with purity above 99% was obtained. The results demonstrate that the combination of polyamide and styrene-divinylbenzene MPC can be utilized for preparative isolation of compounds from natural products with high yield and purity.Dexamethasone is a fluorinated derivative of the natural glucocorticoid, cortisone, with a very high systemic anti-inflammatory effect. In this study, a simple and rapid high performance liquid chromatography (HPLC) method was developed and validated to quantify dexamethasone and its prodrug dexamethasone sodium phosphate in skin permeation studies. The separation of both the compounds was achieved on a Vydac Denali C18 column(250 × 4.6 mm, 5 μm) with a mobile phase composed of 5 mM ammonium acetate buffer-acetonitrile-methanol (433225, v/v) at a flow rate of 0.9 mL/min and UV detection at 240 nm. The standard curves were found to be linear in the range from 0.5 to 100 µg/mL for both the drugs and the method could successfully separate the drug peaks from interfering peaks of endogenous skin constituents. Accuracy values of both the drugs were within 98.60 to 108.60% (intra-day) and 98.70 to 107.20% (inter-day) and precision values were within 2% at the studied concentrations. The developed method was used to investigate the effect of microneedles on transdermal delivery of dexamethasone sodium phosphate.
Read More: https://www.selleckchem.com/products/azd9291.html
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