Simultaneous determination of the bioactive components in rat plasma by UPLC‐MS/MS and application in pharmacokinetic studies after oral administration of radix Scutellariae extract

A highly sensitive and rapid ultraperformance liquid chromatography–tandem mass spectrometry (UPLC‐MS/MS) method has been developed and validated for simultaneous quantification of the four main bioactive compounds, i.e. baicalin, baicalein, wogonoside and wogonin, in rat plasma after oral administration of Radix Scutellariae extract. Clarithromycin was used as an internal standard (IS). Plasma samples were processed by protein precipitation with methanol. The separation was performed on an Acquity BEH C₁₈ column (100 × 2.1 mm, 1.7 μm) at a flow rate of 0.4 mL/min, using 0.1% formic acid–acetonitrile as mobile phase. The MS/MS ion transit ions monitored were 447.5 → 270.1 for baicalin, 270.1 → 168.1 for baicalein, 461.2 → 284.0 for wogonoside, 284.2 → 168.1 for wogonin and 748.5 → 158.1 for IS. Method validation was performed according to US Food and Drug Administration guidelines and the results met the acceptance criteria. The lower limit of quantification (LLOQ) achieved was 1.13 ng/mL for baicalin, 1.23 ng/mL for baicalein, 0.82 ng/mL for wogonoside and 0.36 ng/mL for wogonin. The calibration curves obtained were linear (r > 0.99) over the concentration range ~ 1–1000 ng/mL. The intra‐ and inter‐day precision was <15% and the accuracy was within ±14.7%. After validation, this method was successfully applied to a pharmacokinetic study of Radix Scutellariae extract.     

FLAVONOIDS OF Scutellaria ocellata AND S. nepetoides

The known flavonoids oroxylin A, wogonin, apigenin, 3,7,4'-trihydroxyflavone, cinaroside, baicalin, and wogonoside were isolated from the aerial part ofScutellaria ocellataJuz.; apigenin-7-O--D-glucuronide, norwogonoside, scutellarin, and the new flavoneglycoside nepetoside A, 5,8-dihydroxy-7-O--D-galacturonidopyranosylflavone, from the roots ofScutellaria nepetoidesM. Pop. The structure of the last is established using chemical transformations and spectral data.     

Anti-Photoaging Activity of Scutellaria barbata D. Don (Family Lamiaceae) on Ultraviolet B-Irradiated NIH-3T3 Skin Fibroblast and SKH-1 Hairless Mouse

We investigated whether Scutellaria barbata D. Don (Family Lamiaceae) (SBD), a traditional medicine used for heat clearing and detoxification, possesses antiphotoaging properties. Pretreatment of NIH-3T3 skin fibroblast cells with non-toxicological levels of water extract of SBD (WESBD) and ethanol extract of SBD (EESBD) restored the expression of procollagen type-1 (COL1A1), matrix metalloproteinase-1a (MMP-1a), interleukin-6 (IL-6), interleukin-8 (IL-8), and monocyte chemotactic protein-3 (MCP-3) genes following abnormal expression induced by ultraviolet B (UVB) irradiation. WESBD/EESBD administration to the dorsal skin area of hairless mice significantly (p < 0.05) inhibited UVB-induced wrinkle formation and epidermal thickness. The WESBD and EESBD treatments also restored the dermal collagen content, which was decreased by the UVB treatment, and normal COL1A1 and MMP-1a expression. Interestingly, both the WESBD and EESBD pretreatments significantly attenuated UVB-induced phosphorylation of protein kinase B (AKT) but not that of mitogen-activated protein kinases (MAPKs). This finding indicates that the antiphotoaging effects of WESBD and EESBD may be related to attenuation of UVB-induced overactivation of AKT phosphorylation. High performance liquid chromatography (HPLC) and mass spectrometry analysis revealed that isorhamentin and scutebarbatine I were major single components of EESBD. These results suggest that WESBD and EESBD may have potential in development as antiphotoaging agents.     

Analysis of Flavonoid Metabolites in Watercress (Nasturtium officinale R. Br.) and the Non-Heading Chinese Cabbage (Brassica rapa ssp. chinensis cv. Aijiaohuang) Using UHPLC-ESI-MS/MS

Flavonoids from plants play an important role in our diet. Watercress is a special plant that is rich in flavonoids. In this study, four important watercress varieties were compared with non-heading Chinese cabbage by ultra-high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UHPLC-ESI-MS/MS). A total of 132 flavonoid metabolites (including 8 anthocyanins, 2 dihydroflavone, 3 dihydroflavonol, 1 flavanols, 22 flavones, 11 flavonoid carbonosides, 82 flavonols, and 3 isoflavones) were detected. Flavonoid metabolites varied widely in different samples. Both the non-heading Chinese cabbage and the variety of watercress from Guangdong, China, had their own unique metabolites. This work is helpful to better understand flavonoid metabolites between the non-heading Chinese cabbage and the other four watercress varieties, and to provide a reliable reference value for further research.     

Cyclophanes—VII : Conformations of [2.2](2,5)furanoparacyclophane,[2.2](2,5)furano(1,4)naphthalenophane and [2.2](2,5)furano(9,10)anthracenophane. perpendicularity of aromatic moieties

Variable temperature NMR spectroscopy was used to study the conformational behavior of [2.2](2,5)furanoparacyclophane (1), [2.2](2,5)furano(1,4)naphthalenophane (2) and [2.2](2,5)furano(9,10)anthracenophane (3). While the method was useful in studying 1, it was not adequate for 2 and 3. Variable temperature UV absorption and fluorescence emission studies provided information on the conformations of 2 and 3. The UV absorption and emission spectra of 1 were blue-shifted relative to their ambient temperature spectra. Those of 2 were not shifted at all and those for 3 were red-shifted. The data is consistent with an anti-orientation of the aromatic rings in 2 both at ambient and low temperture. The aromatic rings in 3 are perpendicular to one another at low temperature and probably at room temperature as well. Exiplex bands were absent in the room temperature emission spectra of 1, 2 and 3 as well as the low temperature spectra of 2 and 3. An exciplex band was observed in the low temperature emission spectrum of 1.     

Porphyrins. 38. Reaction of Porphyrins Containing Hydroxy(alkoxy)ethyl or Alkoxymethyl Substituents with Nucleophiles in the Presence of Zinc Acetate. A Novel, Promising Method for the Modification of Porphyrins on the Periphery of the Macrocycle

Porphyrins which contain 1-hydroxy(alkoxy)ethyl or alkoxymethyl substituents on the periphery of the macrocycle (i.e. formally able to yield benzyl type carbocations) react with nucleophiles (4-tert-butylphenol or the -diketones acetylacetone, benzoylacetone, dibenzoylmethane, or 4,4,4-trifluoro-1-(2-thienyl)-1,3-butanedione) in the presence of excess zinc acetate. They give high yields of the corresponding addition products, which are the zinc complexes of porphyrins with a 1-(4-tert-butylphenoxy)ethyl substituent or with substituents containing -diketone residues.     

Novel synthesis of (24R,6E)-24-ethylcholest-6-hydroxyimino-4-en-3-one, a steroidal oxime fromCinachyrella spp. sponges

(24R,6E)-24-ethylcholest-6-hydroxyimino-4-en-3-one (1), which was isolated previously fromCinachyrella spp. sponges, is synthesized in five steps from -sitosterol in 30% overall yield.Institute of Bioorganic Chemistry, National Academy of Sciences of Belarus, Belarus, 220141, Minsk, ul. Akad. Kuprevicha, 5/2. Translated from Khimiya Prirodnykh Soedinenii, No. 2, pp. 149–151, March–April, 2000.     

(E)-1,2-Difluoro-1-iodo-2-trialkylsilanes—A useful synthon for the addition of the [IFCCF] unit to activated electrophiles

Fluoride ion catalyzed reaction of (E)-IFCCFSiR₃ with activated aromatic aldehydes and ketones and activated perfluoroaromatics, such as pentafluoropyridine and perfluorotoluenes, transfers the [IFCCF] unit to the activated electrophiles to stereospecifically provide (E)-1,2-difluoro-1-iodosubstituted derivatives. Aluminum chloride catalyzed reaction of (E)-1,2-difluoro-1-iodo-2-trialkylsilanes with alkyl or aryl acyl halides gives the corresponding (E)-1,2-difluoro-1-iodoketones stereospecifically in excellent yield. The vinyl iodide product formed via this methodology could be coupled (with Pd(0)) catalysis to provide an entry to a polyfunctionalized derivative.     

Assessing the MALDI-TOF MS sample preparation procedure to analyze the influence of thermo-oxidative ageing and thermo-mechanical degradation on poly (Lactide)

Multiple processing by means of successive injection cycles was used to simulate the thermo-mechanical degradation effects on the oligomeric distribution of PLA under mechanical recycling. Likewise, an accelerated thermal ageing over PLA glass transition was performed in order to simulate its service life. MALDI-TOF MS was used for the analysis and the sample preparation procedure was assessed by means of a statistical Design of Experiments (DoE). The quality effects in use for the analysis were signal-to-noise ratio and Resolution. Different matrixes, analyte/matrix proportions and the use of NaTFA as cationization agent were considered. A deep inspection of the statistical results provided a better understanding of the influence of the different factors, individually or in combination, to the signal. The application of DoE for the improvement of the MALDI measurement of PLA stated that the best combination of factors (levels) was the following: matrix (s-DHB), proportion analyte/matrix (1/5 V/V), and no use of cationization agent. Degradation primarily affected the initially predominant cyclic [LA_C]_n and linear H[LA_L]_nOH species, where LA stands for a PLA repeating unit. Intramolecular and intermolecular transesterifications as well as hydrolytic and homolytic reactions took place during the formation and disappearance of oligomeric species. In both degradation mechanisms induced by thermal ageing and thermo-mechanical degradation, the formation of H[LA_L]_nOCH₃ by intermolecular transesterifications was highlighted.