Burchellin and its stereoisomers: total synthesis, structural elucidation and antiviral activity.

Burchellin and its analogues are a class of neolignan natural products containing a rare core with three contiguous stereogenic centers. In previous reports, racemic burchellin was synthesized without accessing each of the enantiomers. In this paper, a concise and efficient total synthetic route to divergently access the enantiomers of burchellin and those of its 1'-epi-diastereoisomer over six steps for each is disclosed, where each of the enantiomers was obtained by preparative chiral phase HPLC purification. The key steps include the construction of a 2,3-dihydrobenzofuran moiety by two Claisen rearrangements and a one-step rearrangement/cyclization and subsequent tandem ester hydrolysis/oxy-Cope rearrangement/methylation to furnish the basic skeleton of burchellin. The structures and absolute configurations of the four stereoisomers were determined using spectroscopic data analyses and comparison of experimental and calculated electronic circular dichroism data. These stereoisomers were found to have potent antiviral effects against coxsackie virus B3, and is the first time that bioactivity has been reported for these compounds.

[Determination of Desloratadine and Its Metabolite 3-OH Desloratadine in Human Plasma by LC-MS/MS].

OBJECTIVE: To develop a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the simultaneous determination of desloratadine and its metabolite 3-OH desloratadine in human plasma. METHODS: 24 healthy male volunteers received a single oral dose of 5 mg desloratadine tablets in a randomized crossover bioequivalence study with two preparations of tablets. Serial plasma samples were taken and analyzed by the LC-MS/MS method. The pharmacokinetic parameters of the two preparations were calculated and compared statistically to evaluate their bioequivalence using Winnonlin 6. 3. RESULTS: The calibration curves of desloratadine and 3-OH desloratadine were both linear over the concentration range of 0. 050-6. 0 ng/mL, with intra-batch and inter-batch relative standard deviations less than 15%. The 90% confidence intervals (CIs) of peak concentration (Cmax) area under the curve (AUC)0t and AUC0-∞ of desloratadine and 3-OH desloratadine all resided within the bioequivalence limit 80%-125%. No significant difference in peak time (Tmax) was demonstrated between the two preparations. CONCLUSION: The LC-MS/MS method can be used for simultaneous determination of desloratadine and 3-OH desloratadine in human plasma, which has been successfully applied-to a bioequivalence study.

[Simultaneous determination of adrenaline, noradrenaline, cortisone and cortisol in plasma with HPLC/MS/MS].

OBJECTIVE: To develop a method for simultaneous determination of adrenaline, noradrenaline, cortisone and cortisol in plasma using HPLC/MS/MS. METHODS: Sample proteins were precipitated with acetonitrile and the sample solution was injected into HPLC/MS/MS after centrifugation at 15,000 r/min for 5 min. Electrospray ionization (ESI) and the positive ion detection were applied with a multiple reaction monitoring (MRM) mode for quantitative analyses. RESULTS: Under the optimal conditions, good linearity (r > 0.999) was observed in the range of 0.02-200.00 ng/mL of target compounds. The detection limit reached 4.13 pg/mL, 4.64 pg/mL, 4.29 pg/mL and 4.52 pg/mL for adrenaline, noradrenaline, cortisone and cortisol respectively. The inter-day and intra-day precisions ranged from 1.19%-5.42% and 2.16%-6.04% respectively. Satisfied results were achieved using human plasma samples, with a spiked recovery in the range of 80.0%-109.0% and a relative standard deviation of 3.93%-7.57%. CONCLUSION: The proposed method is quick, sensitive and suitable for batch analyses of plasma samples.