Pharmacokinetics and tissue distribution study of ginkgolide L in rats by ultra-high performance liquid chromatography coupled with tandem mass spectrometry.

An ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS) approach was developed and validated for the determination of ginkgolide L (GL) in rat plasma and tissues using diazepam as internal standard (IS). Detection was performed on a triple quadrupole MS system using multiple reaction monitoring (MRM) mode in positive mode. Sample preparation was carried out through a liquid-liquid extraction with ethyl acetate. The chromatographic separation was achieved by using an Agilent ZORBAX SB-Aq column with a mobile phase of 0.5% aqueous formic acid (A) and methanol (B). The monitored transitions were set at m/z 391.14→271.10 for GL and m/z 285.08→193.10 for IS, respectively. The validated method was successfully applied to the pharmacokinetic and tissue distribution study of GL in rats after intravenous administration. Good linearity was found between 2.5-2000ng/mL (r>0.996) for plasma samples, and calibration curves were also linear for other tissue samples over a wide range. The results indicated that GL has linear pharmacokinetic properties after intravenous administration at three doses. GL could distribute to tissues quickly and the major distribution tissue of GL in rats was liver. This was the first report of pharmacokinetic and tissue distribution data for GL.

Accurate analysis of ginkgolides and their hydrolyzed metabolites by analytical supercritical fluid chromatography hybrid tandem mass spectrometry.

Hydrolysis plays an important role in the metabolic transformations of lactones. Analysis of lactones and their hydrolyzed metabolites in biological samples is challenging, because unexpected hydrolysis or reversed dehydration may occur depending on the test environments. In this work, a supercritical fluid chromatography hybrid triple-quadrupole mass spectrometry (SFC-QQQ MS) method has been proposed for simultaneous analysis of ginkgolides and hydrolyzed metabolites. The SFC utilizes carbon dioxide as the mobile phase, avoiding hydrolysis of ginkgolides that always happens during reversed phase liquid chromatographic detection. Compared with normal phase liquid chromatography, the SFC provides good resolutions especially for ginkgolide with similar structures. This SFC-QQQ MS method was validated in linearity, precision, accuracy, and stability for ginkgolides and metabolites. Then this method was successfully applied to pharmacokinetic study of 3 ginkgolides and their 6 hydrolyzed metabolites after intravenous administration of total ginkgolide extract. Ginkgolides and metabolites showed different clear rates and excluded in 2-4h. The developed SFC-QQQ MS method allows accurate determination of ginkgolides and metabolites with high resolutions, and can be extended to analysis of other water-unstable compounds.

Daturametelins H, I, and J: three new withanolide glycosides from Datura metel L.

Three new withanolide glycosides named daturametelins H-J (1-3), together with two known ones, daturataturin A (4) and 7,27-dihydroxy-1-oxowitha-2,5,24-trienolide (5), were isolated from the MeOH extract of the aerial parts of Datura metel L. (Solanaceae). Their structures were determined mainly by spectroscopic techniques including 2D-NMR (HMBC, HMQC, (1)H,(1)H-COSY, NOESY) and MS experiments. Compounds 1-5 were tested for their antiproliferative activity towards the human colorectal carcinoma (HCT-116) cell line. The nonglycosidic compound 5 exhibited the highest activity of the tested withanolides, with an IC(50) value of 3.2+/-0.2 microM (Table 3).

PTP1B inhibitors from Ardisia japonica.

In bioassay-directed isolation from the whole plant of Ardisia japonica, sixteen known compounds: chrysophanol (1), physcion (2), oleanolic acid (3), euscaphic acid (4), tormentic acid (5), quercetin (6), quercitrin (7), myricitrin (8), kaempferol 3-O-alpha-L-rhamnopyranoside (9), cyclamiretin A 3-O-alpha--rhamnopyranosyl(1-->4)-beta-D-glucopyranosyl(1-->2)-[beta-D-glucopyranosyl(1-->4)]-alpha-L-arabinopyranoside (10), (7E)-9-hydroxymegastigma-4, 7-dien-3-on-9-O-beta-D-glucopyranoside (11), bergenin (12), norbergenin (13), rutin (14), kaempferol 3,7-O-alpha-L-dirhamnopyranoside (15), (-)-epigallacatechin 3-O-gallate (16) were obtained. Compounds 1-5, 9, 11 and 14-16 have not been reported previously from this plant. Among these isolates, 2, 3, 6 and 12 showed moderate bioactivity against PTP1B in vitro with IC50 values of 121.50, 23.90, 28.12 and 157 microM, respectively.

Furostanoside from Asparagus filicinus.

A new furostanoside, named aspafilioside D (1), together with the five known compounds officinalisnin-II (2), Asp-IV' (3), (+)-4'-O-methyl-nyasol (4), (+)-nyasol (5) and tormentic acid (6), have been isolated from the roots of Asparagus filicinus. The structure of 1 has been elucidated on the basis of spectral data.

Guaiane-type sesquiterpenoids from Alisma orientalis.

Two guaiane-type sesquiterpenoids named orientalol E (1) and orientalol F (3) were isolated from the rhizome of Alisma orientalis (SAM) JUZEP together with two known guaiane-type sesquiterpenoids alismol (2) and alismoxide (4). Their relative stereostructures were elucidated by spectroscopic methods, whereas absolute stereostructures were determined on the basis of chemical correlation.

A flavonol tetraglycoside from Sophora japonica seeds.

A flavonol tetraglycoside, kaempferol 3-O-alpha-L-rhamnopyranosyl(1-->6)-beta-D-glucopyranosyl(1-->2)- beta-D-glucopyranoside-7-O-alpha-L rhamnopyranoside, together with nine known compounds were isolated from the seeds of Sophora japonica L. Their structures were elucidated on the basis of spectral and chemical evidence.

[A new alkaloid from Opuntia vulgaris].

AIM: To study the chemical constituents of the stems of Opuntia vulgaris Mill(Cactaceae). METHODS: The compounds of Opuntia vulgaris were isolated by chromatography of Amberlite Dowex 50 and silica gel, and identified by means of UV, IR, MS, 1D and 2D NMR. RESULTS: Three compounds were isolated and identified as: opuntin B(I), 4-hydroxyproline(II) and tyrosine(III). CONCLUSION: Compound I is a new alkaloid.

Isolation and identification of antioxidants from Sophora japonica.

A new flavonol triglycoside, kaempferol 3-O-alpha-L-rhamnopyranosyl-(1 --> 6)-beta-D-glucopyranosyl-(1 --> 2)-beta-D-glucopyranoside (1), as well as two known kaempferol 3-O-[alpha-L-rhamnopyranosyl-(1 --> 6)]-[beta-D-glucopyranosyl-(1 --> 2)]-beta-D-glucopyranoside (2) and kaempferol 3-O-beta-D-glucopyranosyl-(1 --> 2)-beta-D-glucopyranoside-7-O-alpha-L-rhamnopyranoside (3), were isolated from the n-BuOH extract of the pericarps of Sophora japonica by bioassay-guided fractionation. The structure of compound 1 was established by UV, IR, MS, and one- and two-dimensional NMR spectroscopy, including DEPT, NOESY, DQF-COSY, TOCSY, HMQC, and HMBC experiments. Compounds 1-3 showed antioxidative activity in DPPH and cytochrome-c assay using HL-60 cell system.

A new coumaronochromone from Sophora japonica.

A new coumaronochromone derivative, sophorophenolone (1), along with 13 known compounds, l-maackiain (2), medicagol (3), 7-O-methylpseudobaptigenin (4), pseudobaptigenin (5), 7,3'-di-O-methylorobol (6), genistein (7), prunetin (8), daidzein (9), formononetin (10), Di-O-methyldaidzein (11), quercetin (12), kaempferol (13) and isorhamnetin (14) were isolated from pericarps of Sophorajaponica L. The structure of compound 1 was established by UV, IR, MS, and one-dimensional and two-dimensional NMR spectroscopy, including DEPT, NOESY, 1H-1H COSY, HMQC, and HMBC experiments.