Simultaneous enantiomer determination of 20 (R)- and 20 (S)-ginsenoside-Rg2 in rat plasma after intravenous administration using HPLC method

20 (R,S)-Ginsenoside-Rg2, an anti-shock agent, is prescribed as a racemate. To analyze simultaneously the enantiomers of 20 (R)-ginsenoside-Rg2 and 20 (S)-ginsenoside-Rg2 in plasma, a simple and reproducible high-performance liquid chromatographic (HPLC) method has been developed. The enantiomeric separation and determination were successfully achieved using a Diamonsil ODS C18 reversed-phase column (5 microm, 250 mm x 4.6 mm) with an RP18 (5 microm) guard column and a mobile phase of MeOH-aq. 4% H3PO4 (65:35, v/v, pH 5.1) with UV detection at 203 nm. Both enantiomers, 20 (R)-ginsenoside-Rg2 and 20 (S)-ginsenoside-Rg2, were well separated at 14.5 min and 13.6 min, respectively. The linear ranges of the standard curves were 2.0-250 microg/ml. The intra- and inter-day precision (R.S.D.) were 相似文献   

The effectiveness of a pyriprole (125 mg/ml) and a metaflumizone (150 mg/ml) combined with amitraz (150 mg/ml) spot-on treatment in preventing Phlebotomus perniciosus from feeding on dogs

A controlled clinical trial was performed to assess the effectiveness of a pyriprole (125 mg/ml) and a metaflumizone (150 mg/ml) combined with amitraz (150 mg/ml) spot-on treatment (recommended dosage) in preventing adult female sandflies (Phlebotomus perniciosus) from feeding on dogs. Sandfly mortality was also assessed. Twelve beagle dogs were used in the study. Prior to treatment they were checked for their attractiveness to sandflies, ranked accordingly to generate partner triplets of equivalent sensitivity to sandflies: four control dogs, four treated with the pyriprole and four with the metaflumizone spot-on. The dogs were challenged with 50 unfed adult female sandflies (8-10 days old), in cages for one hour on Day 1 and Day 7. The sandflies were checked for blood feeding and mortality at one hour, 24 hours and 48 hours after exposure to the dogs. A very poor anti-feeding effect (near 7%) was seen on sandflies with the metaflumizone combined with amitraz and no antifeeding effect was seen with pyriprole. The sandfly mortality effect as a result of exposure to treated dogs was under 20% for the two spot-on. The two formulations could not be proposed in a leishmaniosis prevention program.     

Intranasal midazolam in piglets: pharmacodynamics (0.2 vs 0.4 mg/kg) and pharmacokinetics (0.4 mg/kg) with bioavailability determination

Intranasal midazolam was studied in two series of piglets: series 1, n = 20 (18 +/- 3 kg), a randomized double blind pharmacodynamic study to compare doses of 0.2 mg/kg and 0.4 mg/kg; series 2, n = 9 (42 +/- 8 kg), a pharmacokinetic study with a 0.4 mg/kg dose administered either intravenously (i.v.) or intranasally (i.n.) in a cross-over protocol with a one-week wash-out period between each. In series 1, midazolam caused significant anxiolysis and sedation within 3 to 4 min, without a significant difference between 0.2 and 0.4 mg/kg doses for any of the studied parameters. In series 2, after intranasal midazolam administration of 0.4 mg/kg, plasma concentrations attained a maximum (Cmax) of 0.13 +/- 0.04 mg/l at 5 min (median Tmax) and remained higher than 0.04 mg/l until 60 min. The bioavailability factor (F) in this study was F = 0.64 +/- 0.17 by the intranasal route. The terminal half-life (T1/2 lambda z) = 145 +/- 138 min was comparable with the i.v. administration half-life (158 +/- 127 min). In conclusion, optimal intranasal midazolam dose in piglets was 0.2 mg/kg, which procures rapid and reliable sedation, adapted to laboratory piglets.     

Synthesis of (+)-Lasonolide A: (-)-lasonolide A is the biologically active enantiomer

(+)-Lasonolide A was synthesized following the established procedure. (−)-Lasonolide A was found to be the biologically active enantiomer.     

A novel design of simulated moving bed (SMB) chromatography for separation of ketoprofen enantiomer

A simulated moving bed (SMB) chromatography system is a powerful tool for preparative scale separation, which can be applied to the separation of chiral compound. We have designed our own lab-scale SMB chromatography using 5 HPLC pumps, 6 stainless steel columns and 4 multi-position valves, to separate a racemic mixture of ketoprofen in to its enantiomers. Our design has the characteristics of the low cost for assembly for the SMB chromatography and easy repair of the unit, which differs from the designs suggested by other investigators. It is possible for the flow path through each column to be independently changed by computer control, using 4 multi-position rotary valves and 5 HPLC solvent delivery pumps. In order to prove the operability of our SMB system, attempts were made to separate the (S)-ketoprofen enantiomer from a ketoprofen racemic mixture. The operating parameters of the SMB chromatography were calculated for ketoprofen separation from a batch chromatography experiment as well as by the triangle theory. With a feed concentration of 1 mg/mL, (S)-ketoprofen was obtained with a purity of 96% under the calculated operating conditions.     

Metabolic effect at six and twelve months of cyproterone acetate (2 mg) combined with ethinyl estradiol (35 micrograms) in 31 patients

The metabolic effects of cyproterone acetate (2 mg) combined with a new dose level of ethinyl estradiol (35 micrograms) were studied over a one-year period in 31 patients presenting moderate clinical hyperandrogenism. The following tests were performed before treatment, at 6 and 12 months, an oral glucose tolerance test (OGTT) with measurement of insulinemia, total cholesterol, HDL cholesterol and the LDL + VLDL/HDL ratio, A1 and B apoproteins. At six months and at one year of treatment, the weight and body mass index (kg/m2) were not modified. Glucose tolerance and insulinemia had not changed significantly at one year. Lipid test results showed an increase in triglycerides, as well as in total and HDL cholesterol levels. However, the LDL + VLDL/HDL and A1/B apoprotein ratios did not change during the study. We conclude from these results that the new combination does not have any adverse effects on glucose tolerance and has a predominantly estrogenic effect on lipid parameters, characterized by increases in total cholesterol, HDL cholesterol and triglycerides.     

Efficient synthesis of the ketone body ester (R)-3-hydroxybutyryl-(R)-3-hydroxybutyrate and its (S,S) enantiomer

The ketone body ester (R)-3-hydroxybutyryl-(R)-3-hydroxybutyrate and its (S,S) enantiomer were prepared in a short, operationally simple synthetic sequence from racemic β-butyrolactone. Enantioselective hydrolysis of β-butyrolactone with immobilized Candida antarctica lipase-B (CAL-B) results in (R)-β-butyrolactone and (S)-β-hydroxybutyric acid, which are easily converted to (R) or (S)-ethyl-3-hydroxybutyrate and reduced to (R) or (S)-1,3 butanediol. Either enantiomer of ethyl-3-hydroxybutyrate and 1,3 butanediol are then coupled, again using CAL-B, to produce the ketone body ester product. This is an efficient, scalable, atom-economic, chromatography-free, and low cost synthetic method to produce the ketone body esters.     

(1'S)-Acetoxychavicol acetate and its enantiomer inhibit tumor cells proliferation via different mechanisms

Elucidation of the mechanisms underlying potential anticancer drugs continues and unraveling these mechanisms would not only provide a conceptual framework for drug design but also promote use of natural products for chemotherapy. The biological effects of (1'S)-acetoxychavicol acetate ((S)-ACA) have been widely investigated. However, in most cases, a natural product or synthetic racemic compound was used in the study. In this study, we prepared (S)-ACA and its enantiomer (R)-ACA by a lipase-catalyzed esterification method and sought to determine the mechanisms of action of (S)-ACA and (R)-ACA in the growth inhibitory effect in Ehrlich ascites tumor cells (EATC). (S)-ACA caused an accumulation of tumor cells in the G1 phase of the cell cycle, which was accompanied by a decrease in phosphorylated retinoblastoma protein (Rb), an increase in Rb and a decrease in the phosphorylation of p27kip1. However, (R)-ACA caused an accumulation of tumor cells in the G2 phase of the cell cycle, an increase in hyperphosphorylated Rb and an increase in the phosphorylation of p27kip1. The results obtained in the present study demonstrate for the first time, to the best of our knowledge, that both (S)-ACA and (R)-ACA caused the inhibition of tumor cells growth but the inhibition was caused via different mechanisms.     

The monoclonal antibody MAC252 does not react with the (-) enantiomer of abscisic acid

An RIA procedure has been developed for ABA quantification using MAC62, a monoclonal antibody raised against (+)-cis, trans -ABA. This widely used method now relies on MAC252, a recloned version of the exhausted MAC62. Recently, it has been suggested that MAC252 was not able to discriminate between the (+) and (-) enantiomers of ABA. As this can be misleading when interpreting RIA results, it has been carefully examined here whether MAC252 reacts with (-)-ABA. MAC252 exhibited negligible cross-reactivity with (-)-ABA, which was confirmed with commercial mixtures of ABA isomers. It is concluded that the RIA protocol can continue to be used with MAC252 as it was with MAC62.     

Stereoselective covalent binding of anti-benzo(a)pyrene diol epoxide to DNA conformation of enantiomer adducts

The conformation of adducts derived from the reactions and covalent binding of the (+) and (-) enantiomers of 7 beta, 8 alpha-dihydroxy-9 alpha, 10 alpha-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene (anti-BaPDE) with double-stranded calf thymus DNA in vitro were investigated utilizing the electric linear dichroism technique. The linear dichroism and absorption spectra of the covalent DNA complexes are interpreted in terms of a superposition of two types of binding sites. One of these conformations (site I) is a complex in which the plane of the pyrene residue is close to parallel (within 30 degrees) to the planes of the DNA bases (quasi-intercalation), while the other (site II) is an external binding site; this latter type of adduct is attributed to the covalent binding of anti-BaPDE to the exocyclic amino group of deoxyguanine (N2-dG), while site I adducts are attributed to the O6-deoxyguanine and N6-deoxyadenine adducts identified in the product analysis of P. Brookes and M.R. Osborne (Carcinogenesis (1982) 3, 1223-1226). Site II adducts are dominant (approximately 90% in the covalent complexes derived from the (+) enantiomer), but account for only 50 +/- 5% of the adducts in the case of the (-)-enantiomer. The orientation of site II complexes is different by 20 +/- 10 degrees in the adducts derived from the binding of the (+) and the (-) enantiomers to DNA, the long axis of the pyrene chromophore being oriented more parallel to the axis of the DNA helix in the case of the (+) enantiomer. These findings support the proposals by Brookes and Osborne that the difference in spatial orientation of the N2-dG adducts of (-)-anti-BaPDE together with their lower abundance may account for the lower biological activity of the (-) enantiomer. The external site II adducts, rather than site I adducts, appear to be correlated with the biological activity of these compounds.