Seven new 3,4-dihydro-furanocoumarin derivatives from Angelica dahurica / 中草药·英文版

OBJECTIVE@#To study the chemical constituents of the roots of Angelica dahurica, a well-known Chinese herbal medicine named Baizhi in Chinese.@*METHODS@#Compounds were separated by various chromatographies, and the structures of new compounds were elucidated based on the analysis of their spectroscopic and spectrometric data (1D, 2D NMR, HRESI MS, IR, and UV). The absolute configurations of new compounds were determined by the calculated electronic circular dichroism and chemical derivatization. The inhibitory activities of all isolates against nitric oxide (NO) production were evaluated using lipopolysaccharide-activated RAW 264.7 macrophage cells.@*RESULTS@#Seven new 3,4-dihydro-furanocoumarin derivatives ( 1a/ 1b, 2a/ 2b, 3a/ 3b, 4) together with a known furanocoumarin ( 5) were isolated from the roots of A. dahurica. The new compounds included three pairs of enantiomers, (4S, 2''R)-angelicadin A ( 1a)/(4R, 2''S)-angelicadin A ( 1b), (4S, 2''S)-angelicadin A ( 2a)/(4R, 2''R)-angelicadin A ( 2b), and (4S, 2''S)-secoangelicadin A ( 3a)/(4R, 2''R)-secoangelicadin A ( 3b), together with (4R, 2''R)-secoangelicadin A methyl ester ( 4). The known xanthotoxol ( 5) inhibited the NO production with the half-maximal inhibitory concentration (IC50) value of (32.8 ± 0.8) µmol/L, but all the new compounds showed no inhibitory activities at the concentration of 100 µmol/L.@*CONCLUSION@#This is the first report of the discovery of 3,4-dihydro-furanocoumarins from A. dahurica. The results are not only meaningful for the understanding of the chemical constituents of A. dahurica, but also enrich the reservoir of natural products.

Meroterpenoids from Rhododendron nivale / 中国中药杂志

To elucidate the chemical material basis of Rhododendron nivale, this study comprehensively used various chromatographic techniques to isolate and obtain five new meroterpenoid enantiomers(1a/1b-5a/5b) from the ethyl acetate extract of R. nivale. A variety of spectral analytical methods, such as high-resolution mass spectrometry(HRMS), nuclear magnetic resonance spectroscopy(NMR), and infrared(IR) spectrum, were used to evaluate the structure, combined with the measurement and calculation of electronic circular dichroism(ECD). The new compounds 1a/1b-4a/4b were named as(±)-nivalones A-B(1a/1b-2a/2b) and(±)-nivalnoids C-D(3a/3b-4a/4b), along with one known enantiomer(±)-anthoponoid G(5a/5b). Human neuroblastoma cells(SH-SY5Y cells) induced by hydrogen peroxide(H_2O_2) were used as oxidative stress models to evaluate the protective activity of the isolated compounds against oxidative damage to nerve cells. It was found that compounds 2a and 3a had a certain protective effect on nerve cells against H_2O_2-induced oxidative damage at concentrations of 50 μmol·L~(-1), which increased the cell survival rate from 44.02%±2.30% to 67.82%±1.12% and 62.20%±1.87%, respectively. Other compounds did not show a significant ability to protect cells from oxidative damage. These findings enrich the chemical constituents of R. nivale and provide valuable information for identifying the structure of its meroterpenoids.

Enantiomeric characteristics of non-synthetic cannabidiol by two-dimensional nuclear magnetic resonance

SUMMARY Introduction: Cannabidiol (CBD) has become a promising bioactive for the next decades after the recent recognition of the medical potential of Cannabis derivatives by United Nations member countries, as it has no psychotropic potential as your isomer A9-tetrahydrocannabinol (Δ9-THC). The differentiation of these isomers has been studied for decades. Recent studies demonstrate that even with more subtle chemical characteristics, such as those of the CBD enantiomers, there are considerable bioactive differences. However, there are still not many studies on their chemical structures. Aim: This work aims to present experimental data obtained by Nuclear Magnetic Resonance (NMR) to better elucidate the three-dimensional structure of this enantiomeric bioactive. Materials and methods: For this, a sample of non-synthetic high purity CBD was subjected to different one-dimensional (1D-NMR) and two-dimensional (2D-NMR) analyses related to the hydrogen (1H) and carbon (13C) nuclei. Results and discussion: The 1D-NMR techniques used are sufficient to distinguish the CBD and Δ 9-THC isomers, but not to identify the enantiomeric characteristics of the non-synthetic CBD. Conclusions: It is concluded that the two-dimensional homonuclear (1H,1H) and heteronuclear (1H,13C) techniques analyzed are suitable to help distinguish CBD enantiomers.

Introducción: El cannabidiol (CBD) se ha convertido en un bioactivo prometedor para las próximas décadas tras el reciente reconocimiento del potencial medicinal de los derivados del Cannabis por parte de los países miembros de las Naciones Unidas, ya que no tiene potencial psicotrópico como su isómero Δ9-tetrahidrocannabinol (Δ 9-THC). La diferenciación de estos isómeros se ha estudiado durante décadas. Estudios recientes demuestran que incluso con características químicas más sutiles, como las de los enan-tiómeros del CBD, existen diferencias bioactivas considerables. Sin embargo, no existen muchos estudios sobre sus estructuras químicas. Objetivo: Este trabajo tiene como objetivo presentar datos experimentales obtenidos por Resonancia magnética nuclear (RMN) para dilucidar mejor la estructura tridimensional de este bioactivo enantiomérico. Materiales y métodos: Para ello, una muestra de CBD no sintético de alta pureza se sometió a diferentes análisis unidimensionales (RMN-1D) y bidimensionales (RMN-2D) relacionados con los núcleos del hidrógeno (1H) y carbono (13C). Resultados y discusión: Las técnicas de RMN-1D utilizadas son suficientes para distinguir los isómeros de CBD y Δ 9-THC, pero no para identificar las características enantioméricas del CBD no sintético. Conclusiones: Se concluye que las técnicas bidimensionales homonucleares (1H,1H) y heteronucleares (1H,13C) analizadas son adecuadas para ayudar a distinguir los enantiómeros del CBD.

Introdução: O canabidiol (CBD) se tornou um bioativo promissor para as próximas décadas após o recente reconhecimento do potencial medicinal dos derivados da Cannabis pelos países membros das Nações Unidas, uma vez que não tem potencial psicotrópico como seu isômero Δ 9-tetrahidrocanabinol (A9-THC). A diferenciação desses isômeros é estudada há décadas. Estudos recentes demonstram que mesmo com características químicas mais sutis, como as dos enantiômeros do CBD, há consideráveis diferenças bioativas. Todavia, ainda não há muitos estudos sobre suas estruturas químicas. Objetivo: Este trabalho tem como objetivo apresentar dados experimentais obtidos por Ressonância magnética nuclear (RMN) para melhor elucidar a estrutura tridimensional deste bioativo enantiomérico. Materiais e métodos: Para isso, uma amostra de CBD não sintético de alta pureza foi submetida a diferentes análises unidimensionais (RMN-1D) e bidimensionais (RMN-2D) relacionadas aos núcleos de hidrogênio (1H) e carbono (13C). Resultados e discussão: As técnicas de RMN-1D usadas são suficientes para distinguir os isômeros CBD e Δ 9-THC, mas não para identificar as características enantioméricas do CBD não sintético. Conclusões: Conclui-se que as técnicas bidimensionais homonucleares (1H,1H) e heteronucleares (1H,13C) analisadas são adequadas para auxiliar na distinção dos enantiômeros do CBD.

A pair of new phenylpropanoid enantiomers from Cordia dichotoma fruits / 药学学报

The ethyl acetate part of the alcoholic extract of Cordia dichotoma fruits was purified by a combination of normal-phase silica gel column chromatography, Sephadex LH-20 gel column chromatography and semi-preparative HPLC, and the structure was identified by modern spectroscopic techniques (UV, IR, MS, NMR). A total of 10 compounds were isolated and identified as cordilide (1), (S)-2-hydroxy-3-(4′-hydroxyphenyl) propanoic acid (2), vanillic acid (3), p-coumaric acid (4), 3-hydroxy-1-(4-hydroxy-3-methoxyphenyl)propan-1-one (5), benzoic acid (6), p-hydroxypropiophenone (7), p-hydroxyacetophenone (8), 5′-methoxyevofolin B (9) and vanillin (10). Among them, compound 1 is a pair of new phenylpropanoid enantiomers, and compounds 3, 6, 8 and 9 were isolated for the first time from the genus.

Equol and its enantiomers inhibited urethane-induced lung cancer in mice / 北京大学学报(医学版)

OBJECTIVE@#To investigate the effects and mechanisms of equol and its enantiomers on urethane-induced lung cancer in mice.@*METHODS@#A total of 120 5-week-old male C57BL/6 mice were randomly divided into 8 groups: lung cancer tumor control group (CG), genistein control group (GCG), low dose racemic equol group (LEG), high dose racemic equol group (HEG), low dose R-equol group (LRE), high dose R-equol group (HRE), low dose S-equol group (LSE) and high dose S-equol group (HSE). Urethane was injected subcutaneously twice a week for 4 weeks to induce lung cancer and then the mice were fed for 4 months. The body weight and food intake of each group were measured and recorded weekly. After the mice were sacrificed, the blood, livers and lungs of the mice were collected. The incidence of lung cancer in each group was recorded. The concentration of serum superoxide dismutase (SOD), malondialdehyde (MDA) and 8-hydroxydeoxygunosine (8-OHdG) were detected by the corresponding kits. Western blotting was used to detect the expression of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) in the livers. Between-group differences in body weight and food intake of the mice were compared using repeated measures ANOVA, and ANOVA for the differences between non-repeated measurements, with post hoc analysis using Tukey's method if there were between-group differences. Comparisons of categorical data were performed by chi-square test, and if there were differences between the groups, the Bonferroni method was used for pairwise comparison.@*RESULTS@#A total of 49 in the 120 mice developed lung cancer. The overall incidence of lung cancer was 40.8%. Compared with the control group, the incidence of lung cancers in each experimental group was lower, and the difference was statistically significant. The incidence of lung cancer in the high-dose experimental group was significantly lower than that in the low-dose experimental group. However, the incidence of lung cancer was similar in the three equol groups and the genistein group at the same dose. Compared with the control group, the high-dose experimental group had higher serum SOD concentration, lower MDA and 8-OHdG concentrations, and the differences were statistically significant. Western blotting analysis showed that the expression levels of Nrf2 protein in the experimental groups were higher than those in the control group except the low-dose racemic equol group, and the Nrf2 protein expression level in the high-dose equol groups was higher than that in the low-dose equol groups.@*CONCLUSION@#Racemic equol and its enantiomers mayinhibit lung carcinogenesis through antioxidant effects.

Single-run reversed-phase HPLC method for determining sertraline content, enantiomeric purity, and related substances in drug substance and finished product / 药物分析学报

A direct enantio-, diastereo-, and chemo-selective high-performance liquid chromatographic method was developed for determining the content, enantiomeric purity, and related substances of the chiral antidepressant drug sertraline HCl in a single chromatographic run. The separation was achieved on a chiral stationary phase based on amylose tris(3-chloro-5-methylphenylcarbamate) under reversed-phase conditions. The method was optimized by evaluating the influence of the temperature and mobile phase composition on the retention and selectivity. The application of the single-run approach allowed to baseline resolve all investigated species in less than 15 min, without using buffers or tandem-coupled columns. The chromatographic method was validated according to the guidelines of the Official Medi-cines Control Laboratory and applied to control the content of sertraline HCl and related chiral sub-stances in a generic antidepressant formulation.

A pair of enantiomeric sesquiterpenoids with neuroprotective effects from Chloranthus henryi / 药学学报

An ethanol extract of Chloranthus henryi (Chloranthaceae) was subjected to various chromatographic procedures including silica gel column chromatography, MCI column chromatography, Sephadex LH-20 column chromatography, and preparative HPLC. Five purified sesquiterpenes analyzed by spectroscopic analyses (MS, IR, NMR) and single crystal X-ray diffraction were elucidated as (1S,6S,8R)-8-ethoxychlomultin C (1a), (1R,6R,8S)-8-ethoxychlomultin C (1b), (+)-phaeocaulin D (2), atractylenolide Ⅰ (3), and 8-β-ethoxyasterolid (4). Compounds 1a and 1b were a new pair of sesquiterpene enantiomers and compounds 2-4 were isolated from this plant for the first time. Compounds 1a, 1b, 2 and 3 increased cell viability in H2O2-treated PC12 cells from (43.41 ± 1.59) % to (61.71 ± 7.56) %, (66.05 ± 5.61) %, (74.34 ± 3.32) % and (69.58 ± 5.02) % at 10 μmol·L-1, respectively.

Enantiomeric pairs of meroterpenoids from Rhododendron fastigiatum / 中国天然药物

Five pairs of optically pure meroterpenoid enantiomers (1a/1b-5a/5b) and two known compounds (6 and 7) were isolated from Rhododendron fastigiatum. Compounds 1a/1b-5a/5b were resolved from naturally scalemic mixtures by chiral HPLC. Their structures were elucidated by spectroscopic methods, X-ray crystallographic experiments, and ECD analyses. Compounds 1a/1b, 2a/2b, 3b, 4a/4b, and 5a/5b were new meroterpenoids with different polycyclic systems. Two enantiomeric pairs (2a/2b and 3a/3b), 6, and 7 exhibited inhibitory effects on protein tyrosine phosphatase 1B (PTP1B) in vitro.

Performance comparison of chlorinated chiral stationary phases in supercritical fluid chromatography for separation of selected pyrrolidone derivatives / 药物分析学报

The effects of two chlorinated chiral stationary phases, namely, Lux Cellulose-2 and Lux i-Cellulose-5, flow-rate, percentage of co-solvent and chemical structures of the compounds on retention and reso-lution were studied within this article. In this work a backpressure of 150 bar, a temperature of 40 ℃ and 10％ of methanol as co-solvent were chosen as operating conditions. The optimum flow-rate was 2 mL/min. The percentage of co-solvent was studied between 7.5％ and 15％. We have observed that 15％ of methanol gave the best results for most of the compounds. For all the derivatives, the Lux Cellulose-2 provided better resolutions going from 1.50 to 3.59 compared with Lux i-Cellulose-5.

Preparation and application of novel polysulfone chiral membranes for the separation of tryptophan enantiomers / 中国药科大学学报

@#To preparate a novel polysulfone chiral membranes, β-cyclodextrin was functionalized with dodecanoyl chloride, and this modified β-cyclodextrin was then incorporated into polysulfone casting solution to form the dodecanoyl-β-cyclodextrin/polysulfone chiral membrane. Meanwhile, current studies have investigated the effect of adding different amount of dodecanoyl-β-cyclodextrin on the pure water flux, bovine serum albumin(BSA)rejection rate and enantioselectivity of the membranes. The morphology of the dodecanoyl-β-cyclodextrin/polysulfone chiral membrane was characterized by scanning electron microscopy(SEM). With the incorporation of dodecanoyl-β-cyclodextrin, the pore structure of the membrane changed significantly, with more finger-like pore structures appearing in the support layer. So the membrane water flux increased significantly, while the BSA rejection rate decreased. When the addition amount of dodecanoyl-β-cyclodextrin was in the range of 2% to 3. 5%, the enantiomeric excess increased with the addition of dodecanoyl-β-cyclodextrin. A complete separation of racemic tryptophan can be performed using this novel dodecanoyl-β-cyclodextrin/polysulfone chiral membrane-based separation system.

Separation and determination of acetyl-glutamine enantiomers by HPLC–MS and its application in pharmacokinetic study / 药物分析学报

A high-performance liquid chromatography coupled with mass spectrometry (HPLC–MS) method was established for the separation and determination of acetyl-glutamine enantiomers (acetyl-L-glutamine and acetyl-D-glutamine) simultaneously. Baseline separation was achieved on Chiralpak AD-H column (250 mm × 4.6 mm, 5 μm). n-Hexane (containing 0.1% acetic acid) and ethanol (75:25, v/v) were used as mobile phase at a flow rate of 0.6 mL/min. The detection was operated in the negative ion mode with an ESI source. [M-H]? m/z 187.0540 for enantiomers and [M-H]? m/z 179.0240 for aspirin (IS) were selected as detecting ions. The linear range of the calibration curve for each enantiomer was 0.05–40 μg/mL. The precision of this method at concentrations of 0.5–20 μg/mL was within 7.23%, and the accuracy was 99.81%–107.81%. The precision at LOQ (0.05 μg/mL) was between 16.28% and 17.56%, which was poor than that at QC levels. The average extraction recovery was higher than 85% for both enantiomers at QC levels. The pharmacokinetics of enantiomers was found to be stereoselective. There was not chiral inversion in vivo or in vitro between enantiomers.

Separation and determination of acetyl-glutamine enantiomers by HPLC–MS and its application in pharmacokinetic study / 药物分析学报

A high-performance liquid chromatography coupled with mass spectrometry (HPLC–MS) method was established for the separation and determination of acetyl-glutamine enantiomers (acetyl-L-glutamine and acetyl-D-glutamine) simultaneously. Baseline separation was achieved on Chiralpak AD-H column (250 mm × 4.6 mm, 5 μm). n-Hexane (containing 0.1% acetic acid) and ethanol (75:25, v/v) were used as mobile phase at a flow rate of 0.6 mL/min. The detection was operated in the negative ion mode with an ESI source. [M-H]? m/z 187.0540 for enantiomers and [M-H]? m/z 179.0240 for aspirin (IS) were selected as detecting ions. The linear range of the calibration curve for each enantiomer was 0.05–40 μg/mL. The precision of this method at concentrations of 0.5–20 μg/mL was within 7.23%, and the accuracy was 99.81%–107.81%. The precision at LOQ (0.05 μg/mL) was between 16.28% and 17.56%, which was poor than that at QC levels. The average extraction recovery was higher than 85% for both enantiomers at QC levels. The pharmacokinetics of enantiomers was found to be stereoselective. There was not chiral inversion in vivo or in vitro between enantiomers.

Enantiomeric Separation of Three Kinds of Aromatic Amino Acids by C18 Column Tandem Crown Ether Chiral Column / 分析化学

A reversed phase high performance liquid chromatographic ( RP-HPLC ) method was proposed by using C18 column tandem crown ether chiral column for simultaneous separation of three kinds of aromatic amino acid enantiomers. The chromatographic conditions, including mobile phase proportion, pH, column temperature and flow rate, were optimized. The experimental results showed that the three aromatic amino acid enantiomers could be successfully separated under the optimal conditions such as perchloric acid solution-acetonitrile ( 86:14, V/V, pH = 2 ) as mobile phase, column temperature of 20℃ and flow rate of 0. 4 mL/min. The separation under four HPLC column connection modes was further investigated. The results revealed that different kinds of amino acids could be separated on C18 column, but not for amino acid enantiomers; amino acid enantiomers could be separated on crown ether chiral column, but the chromatographic peaks of each amino acid enantiomers overlapped seriously; baseline separation of three amino acid enantiomers could be obtained under the connection of two columns, but the separation under different column connection sequence almost had no difference except the peak shape.

Residue Determination of cis-Epoxiconazole Enantiomers in Fruit and Tea by Ultra Performance Convergence Chromatography Combined with Quadrupole Time-of-Flight Mass Spectrometry / 分析化学

Abstract A chiral separation and residue determination method for cis-epoxiconazole enantiomers in apple, grape and tea samples was developed and validated by ultra performance convergence chromatography combined with quadrupole time-of-flight mass spectrometry ( UPC2-QTOF/MS) . The Chrial CCA column was used to separate cis-epoxiconazole enantiomers and the chromatography conditions ( mobile phase modifier and proportion, column temperature, automated backpressure regulator, and auxiliary solvent ) were optimized. Samples were extracted by acetonitrile, and respectively purified by Cleanert TPT or Pesti-Carb solid phase extraction ( SPE ) columns, then analyzed by UPC2-QTOF/MS. The optimum conditions were as follows:mobile phase was CO2/isopropanol (95: 5, V/V), flow-rate was 2. 0 mL/min, automated backpressure regulator (ABPR) was 13. 79 MPa, column temperature was 30℃, with a post-column mauxiliary solvent of methanol/water (1:1, V/V) containing 2 mmol/L ammonium formate. The analyte was quantified by matrix external standard method. The results showed that linear range of this method was 0. 01-1. 00 mg/L, and the correlation coefficients were above 0 . 99 . The recoveries of cis-epoxiconazole enantiomers at three spiked levels (0. 005, 0. 025 and 0. 25 mg/kg) in fruit matrix were 67. 9%-92. 8% with relative standard deviations (RSDs, n=6) less than 10%, and the limit of quantification (LOQ) of enantiomers was 0. 005 mg/kg. The recoveries of cis-epoxiconazole enantiomers at three spiked levels (0. 01, 0. 05 and 0. 5 mg/kg) in black tea were 74 . 1% -84 . 0% with RSDs ( n=6 ) less than 8%, and the LOQ for these two enantiomers was 0. 01 mg/kg. This method is rapid, convenient and reliable, and could meet the requirement of residue analysis.

Theoretical calculation of electronic circular dichroism: A promising tool for the determination of absolute configuration of natural products / 国际药学研究杂志

Determination of the absolute configuration is one of the most important and long-standing issues in the structure elucidation of natural products. Some natural products have difficulty forming crystal structures or yield few crystal structures, making it impossible to determine their absolute configuration by X-ray diffraction (XRD) and chemical derivatization such as Mosher reaction. Circular dichroism (CD) can be measured in solution, needs only small amount of sample, requires no standards and can be recycled after measurement, so the absolute configurations of chiral natural products can be determined reliabley by comparison of electronic circular dichroism (ECD) spectra with experimental CD spectra. In this paper, we attempt to use the bioactive natural product found by our group, (-)-alternarlactam, together with its synthetic by-product (+)-alternarlactam, to help us understand the applicability of this approach in determining the absolute configurations of complex chiral natural molecules.

Stereoselective pharmacokinetics of itraconazole enantiomers in rats / 中国药科大学学报

@#To investigate the stereoselective pharmacokinetics of itraconazole enantiomers in rats, four cis-ITR stereoisomers at the dose of 15 mg/kg were administered orally to rats. Blood was collected and single stereoisomer of ITZ and hydroxy-itraconazole(OH-ITZ)were determinated simultaneously by LC-MS/MS. Samples were extracted by protein precipitation with acetonitrile. Durashell HILIC column(100 mm×2. 1 mm, 5. 0 m)was used as the analytical column, while a mixture of solvent A(0. 02% acetic acid and 5 mmol/L ammonium acetate in water)and B(50% acetonitrile and 50% methyl alcohol)was used as the mobile phase. A 5. 5 min binary gradient elution(delivered at 0. 5 mL/min)was performed for the separation. LC-MS/MS was performed in positive ion mode with multiple reactions monitoring(MRM). The pharmacokinetic parameters of itraconazole enantiomers after the administration were estimated as follows: the plasma levels and AUC0-∞ of OH-(2S, 4R, 2R)-ITZ and OH-(2S, 4R, 2S)-ITZ were higher than those of OH-(2R, 4S, 2R)-ITZ and OH-(2R, 4S, 2S)-ITZ(P< 0. 001). At the same time, female rats exhibited greater cmax, t1/2, AUC0-∞ than male rats, and the absorption of male rats was more rapid than those of females. The findings indicate significant stereoselective differences in the pharmacokinetic parameters of itraconazole enantiomers and gender difference in rats.

Vailidation of a LC-MS/MS method for quantification of ibuprofen enantiomers in Beagle dog plasma / 中国药理学通报

Aim To develop a simple,rapid and ac-curate analysis method for determination of chiral ibu-profen in Beagle dog plasma.Method The plasma sample was submitted to liquid - liquid extraction u-sing hexane /isopropanol (95 ∶5,V/V),with ketopro-fen as the internal standard (IS).The separation was accomplished in a Lux 5u Cellulose-3 (250 mm·4.6 mm,5 μm)column,and the mobile phase consisted of methanol and a mixture of 1 mmol·L -1 ammonium acetate-methanol-formic acid (90 ∶1 0 ∶0.2,V/V/V) with the volume ratio of 82 ∶1 8 at a flow rate of 0.8 mL· min -1 .The mass spectrometer consisted of an ESI interface operating at negative ionization mode and the detection was performed using multiple reaction monitoring at the transitions of m /z 205.2 /1 61 .2 for ibuprofen and m /z 253.1 /209.2 for ketoprofen (IS). Method validation included the evaluation of the matrix effect, extraction recovery, linearity, lower LOQ, within-run and between-run precision,stability and di-lution effect.Results The calibration curve was line-ar across the concentration range of 0.2 ~50 mg·L -1 for each ibuprofen enantiomer with a lower LOQ of 0.2 mg·L -1 .The within-run and between-run precision (RSD%)was in the range 1 .01 % ~1 3.1 % for each ibuprofen.The pharmacokinetic parameters for orally single dose of (S +)and racemic ibuprofen in Beagle dogs were as follows: Cmax , T1 /2 , AUC(0-t) were (82.98 ±1 4.83 )mg·L -1 ,(3.21 7 ±0.7298)h, (362.0 ±58.67)h·mg·L -1 for (S +)ibuprofen and 70.62 /74.48 mg·L -1 ,1 .520 /5.432 h ,1 77.8 /649.6 h·mg·L -1 for (R -)/(S +)ibuprofen,re-spectively.Conclusions A simple,rapid,accurate, high sensitivity and repeatability method has been suc-cessfully developed,which can analyze the concentra-tions of (R -)/(S +)ibuprofen in Beagle dog plasma simultaneously.The method could be applied for the investigation of pharmacokinetics of ibuprofen enanti-omers in Beagle dogs.

Chiral resolution of ondansetron hydrochloride enantiomers by high performance liquid chromatography / 中国药学杂志

OBJECTIVE: To establish a fast and efficient HPLC method for the chiral separation of ondansetron hydrochloride and determination of the enantiomic impurity of (-)ondansetron(R)hydrochloride.