Xiaohong Liu

Shenyang Pharmaceutical University, Shenyang, Liaoning, China

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Publications (23)50.35 Total impact

  • Article: Nimodipine nanocrystals for oral bioavailability improvement: Preparation, characterization and pharmacokinetic studies.
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    ABSTRACT: This study intended to develop nimodipine (NMD) nanocrystals with different sizes for oral administration and to investigate the relationship between dissolution and pharmacokinetics for NMD nanocrystals and Nimotop(®). NMD nanocrystals were prepared by combination of microprecipitation and high pressure homogenization and were further lyophilized. The particle size, morphology and aqueous solubility of the NMD nanocrystals were determined. With Nimotop(®) as the control, the dissolution rate was evaluated and the pharmacokinetic study was undertaken in beagle dogs. NMD nanocrystals with mean diameters of about 159.0, 503.0 and 833.3nm were prepared, respectively. The lyophilization didn't affect the particle sizes of the redispersed nanocrystals. The aqueous solubility was significantly improved and displayed a size-dependent manner. The nanocrystals exhibited lower dissolution patterns than Nimotop(®) under non-sink condition, but bioavailability of the two nanocrystals (159.0 and 833.3nm) was equivalent, about 2.6-fold higher than Nimotop(®). In conclusion, oral nanocrystal drug delivery system was a promising strategy in improving the oral bioavailability of poorly soluble or insoluble drugs. But we could not establish a favorable in vitro in vivo correlation for NMD nanocrystals and Nimotop(®) and thus the oral absorption mechanism of the NMD nanocrystals required further study.
    Colloids and surfaces. B, Biointerfaces 03/2013; 109C:161-166. · 2.60 Impact Factor
  • Article: Nimodipine nanocrystals for oral bioavailability improvement (part II): role of mesenteric lymph transport in the oral absorption.
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    ABSTRACT: PURPOSE: We had conducted a comprehensive study on preparation, characterization and pharmacokinetics of nimodipine nanocrystals for oral administration previously, and nimodipine nanocrystals displayed lower dissolution profiles but higher bioavailability than Nimotop(®). In this study, we aimed to elucidate the reasons of unfavourable in vitro in vivo correlation for NMD nanocrystals and Nimotop(®) with a hypothesis that special oral absorption mechanism was involved in the absorption of nimodipine nanocrystals. METHODS: Investigations of oral absorption mechanism of the nanocrystals were performed on everted gut sac models, lymphatically (mesenteric lymph duct) cannulated SD rats, Caco-2 cell monolayers and chylomicron flow blocking rats, respectively. RESULTS: The permeability of nanocrystals in duodenum, ileum and colon was not superior to that of Nimotop(®), suggestive of special absorption mechanisms involved. Exudates of nanocrystals from enterocytes were detected in mesenteric lymphatic fluids using a transmission electron microscope, and the bioavailability was only about half of the control after the mesenteric lymph was blocked. The nanocrystals were taken up by enterocytes via macropinocytosis and caveolin-mediated endocytosis pathways. CONCLUSIONS: It was impossible to establish a favorable in vitro in vivo correlation for NMD nanocrystals and Nimotop(®), because portions of the nanocrystals underwent macropinocytosis and caveolin-mediated endocytosis by enterocytes as intact nanocrystal forms, then bypassed the liver first-pass metabolism.
    International journal of pharmaceutics 02/2013; · 2.96 Impact Factor
  • Article: UPLC-MS-MS Method for the Determination of N-(2,6-Dimethoxypyridine-3-yl)-9-methylcarbazole-3-sulfonamide in Rat Plasma and Its Application to a Pharmacokinetic Study
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    ABSTRACT: The purpose of the study is first to develop a sensitive and rapid ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS-MS) method for the determination of a new synthesized tubulin ligand, N-(2,6-dimethoxypyridine-3-yl)-9-methylcarbazole-3-sulfonamide (IG-105), in rat plasma. The analyte and internal standard (carbamazepine) were extracted by liquid/liquid extraction with petroleum ether/diethyl ether (2:1, v/v). The chromatographic separation was performed on an Acquity UPLC BEH C18 column with a mobile phase gradient consisting of methanol and water. The mass spectrometric detection was performed by triple-quadrupole mass spectrometry with multiple reaction monitoring (MRM) via an ESI source operating in positive ionization mode. The mass transitions m/z 398→153 and m/z 237→194 were used to assay the analyte and IS, respectively. The method demonstrated good linearity over a concentration range of 0.67–333.33ngmL−1, and the lower limit of quantitation (LLOQ) of IG-105 was 0.67ngmL−1. The intra- and inter-day precision (relative standard deviation) values were <6%, and the accuracy (relative error) was <5% at three quality control levels. The extraction recovery of IG-105 and IS was 84.45 and 88.5%, respectively. Finally, the validated method was successfully applied to a pharmacokinetic study of IG-105 in rat plasma. KeywordsUPLC-MS-MS–IG-105–Rat plasma–Pharmacokinetic study
    Chromatographia 04/2012; 74(3):327-331. · 1.20 Impact Factor
  • Article: Determination of Armillarisin A in Rat Plasma by SPE and LC-MS-MS
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    ABSTRACT: A rapid, sensitive and convenient ultra-performance liquid chromatography-tandem mass spectrometry method was developed and validated for the determination of armillarisin A in rat plasma. Following hydrophilic–lipophilic balance solid-phase extraction, armillarisin A and propylparaben (internal standard) were separated using a gradient elution program on a C18 column and detected by mass spectrometry in the negative ion mode with the multiple reaction monitoring mode. The total chromatographic running time was short (1.8min). The method was linear over the concentration range of 0.5–250.00ngmL−1 for armillarisin A. The lower limit of quantification of armillarisin A was 0.5ngmL−1, using as little as 100μL plasma. The intra-day and inter-day relative standard deviations were less than 15% and the relative errors were all within 10%. The extraction recovery for armillarisin A was approximately 100%, and no absolute matrix effect was observed. Finally, the method was successfully applied to a preclinical pharmacokinetic study of armillarisin A in four rats following an intravenous administration.
    Chromatographia 04/2012; 70(7):1233-1237. · 1.20 Impact Factor
  • Article: Screening and Identification of Permeable Components of Radix et Rhizoma Rhei Extract by Use of Immobilized Artificial Membrane Chromatography
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    ABSTRACT: The objective of this work was to screen and identify permeable components of Radix et Rhizoma Rhei extract by use of immobilized artificial membrane chromatography (IAMC) then to investigate the intestinal absorption behavior of these components and the mechanism of absorption at three concentrations (0.3, 0.6, and 1.5mgmL−1) by use of the in situ rat intestinal absorption model. The percentage absorption of permeable components was then correlated with their retention behavior by using mobile phases of three different pH (5.0, 6.0, and 7.0) containing buffers of two different ionic strength (10 and 50mmolL−1). There was better correlation between percentage intestinal absorption and IAMC retention at pH 6.0 (r 2=0.82) than at pH 5.0 (r 2=0.64) or 7.0 (r 2=0.74). The correlation coefficients suggest that most of the permeable components of Radix et Rhizoma Rhei were mainly absorbed by a passive diffusion mechanism. The four main permeable components were identified as rhein, aloe-emodin, chrysophanol, and emodin by comparison of chromatographic and spectrometric behavior with those of reference standards. IAMC seems useful as a promising rapid screening technique for identification of bioactive components in complex systems, e.g. traditional Chinese medicines.
    Chromatographia 04/2012; 70(9):1321-1326. · 1.20 Impact Factor
  • Article: UPLC for the Determination of Clopidogrel in Dog Plasma by Tandem Quadrupole MS: Application to a Pharmacokinetic Study
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    ABSTRACT: A rapid, sensitive and specific ultra performance liquid chromatography-electrospray ionization tandem quadrupole mass spectrometry method was developed and validated for the determination of clopidogrel in dog plasma. Plasma samples were deproteinized with acetonitrile and separated on a Waters BEH C18 column (1.7μm, 50mm×2.1mm id.) with isocratic elution at a flow-rate of 0.2mLmin−1 and mobile phase consisting of acetonitrile and water (containing 0.15% formic acid) (75:25, v/v). The single run analysis was as shorter as 2min. Electrospray ionization in positive ion mode and multiple reaction monitoring were used for the quantification of clopidogrel with monitored transitions m/z 322→212 for clopidogrel and m/z 324→217 for internal standard (gliclazide). The intra- and inter-day precisions (RSD%) were less than 6.32 and 7.03%, and accuracy (RE%) between −9.12 and 9.65% (n=6). The extraction recovery of clopidogrel was 96.7%. The developed method was successfully applied to the pharmacokinetic study of clopidogrel tablets in dogs following oral administration at a single dose of 75mg.
    Chromatographia 04/2012; 70(1):259-263. · 1.20 Impact Factor
  • Article: Considerations in the development of an in vitro dissolution condition for lacidipine tablets: in vivo pharmacokinetic evaluation.
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    ABSTRACT: In this study, a new discriminative dissolution condition for lacidipine tablets was developed by the established in vitro-in vivo relationship. Series of dissolution media of phosphate buffer solution (PBS) covering the pH range of 1-7.2 and pH 6.8 PBS containing different concentrations of sodium dodecyl sulfate (SDS), were prepared and used to investigate the dissolution behavior of lacidipine tablets. There was an obvious difference in the dissolution profiles of the both brands in pH 6.8 PBS medium containing 0.1% SDS. The pharmacokinetic study of the two lacidipine tablets was carried out in the healthy beagle dogs at a single dose of 4 mg. Statistical comparison of the AUC(0-24), C(max), and T(max) showed a significant difference in the two brand tablets, coinciding with the dissolution performance with pH 6.8 PBS containing 0.1% SDS. The superiority of the proposed system, pH 6.8 PBS containing 0.1% SDS, could serve as a dissolution medium for lacidipine tablets, and more important it could discriminate the in vivo pharmacokinetic behavior for different brands of products. In summary, in vivo pharmacokinetic evaluation is essential to develop an appropriate in vitro dissolution condition for oral solid dosage forms of poorly soluble drugs.
    Drug Development and Industrial Pharmacy 12/2011; 38(9):1099-106. · 1.49 Impact Factor
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    Article: Factors affecting particle size of an intravenous fat emulsions
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    ABSTRACT: Purpose: To study factors affecting the particle size and particle size distribution of drug-free submicron oil-in-water (O/W) emulsion, including homogenization pressure, temperature, cycle number, pH and steam sterilization conditions, etc. Methods: Piston-gap homogenizer and microfluidizer were used to prepare the intravenous fat emulsions. Samples were collected at different conditions and particle sizes of the emulsion were evaluated by laser diffraction (LD). Results: Both nanosized machines were suitable for the preparation of intravenous fat emulsions and the microfluidizer was more effective than the piston-gap homogenizer in producing smaller particle size and narrower size distribution with less cycle numbers under medium and high homogenization pressure. Additionally, increase in homogenization temperature moderately decreased particle size at low homogenization pressure. However, this influence wasn't obvious under the high homogenization pressure. The pH values did not significantly alter the emulsion particle size, and steam sterilization slightly caused an increase in particle size. Conclusions: Ranking the various factors investigated was as follows: homogenization pressure ≈ number of cycles > homogenization temperature > stream sterilization > pH values.
    Asian Journal of Pharmaceutical Sciences 01/2010; 5:161-167.
  • Article: Solid self-emulsifying nitrendipine pellets: preparation and in vitro/in vivo evaluation.
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    ABSTRACT: Objective of this study is to develop and evaluate the new solid self-emulsifying (SE) pellets of poorly soluble nitrendipine (NTD). These pellets were prepared via extrusion/spheronization technique, using liquid SEDDS (NTD, Miglyol 812, Cremophor RH 40, Tween 80, and Transcutol P), adsorbents (silicon dioxide and crospovidone), microcrystalline cellulose and lactose. The resulting SE pellets with 30% liquid SEDDS exhibited uniform size (800-1000 microm) and round shape, droplet size distribution following self-emulsification was nearly same to the liquid SEDDS (72+/-16 nm and 64+/-12 nm). The in vitro release was similar for the two SE formulations (over 80% within 30 min), both significantly higher than the conventional tablets (only 35% within 30 min). The oral bioavailability was evaluated for the SE pellets, liquid SEDDS and conventional tablets in fasted beagle dogs. AUC of NTD from the SE pellets showed 1.6-fold greater than the conventional tablets and no significant difference compared with the liquid SEDDS. In conclusion, our studies illustrated that extrusion/spheronization technique could be a useful large-scale producing method to prepare the solid SE pellets from liquid SEDDS, which can improve oral absorption of NTD, nearly equivalent to the liquid SEDDS, but better in the formulation stability, drugs leakage and precipitation, etc.
    International journal of pharmaceutics 09/2009; 383(1-2):1-6. · 2.96 Impact Factor
  • Article: Prediction of volume of distribution values in human using immobilized artificial membrane partitioning coefficients, the fraction of compound ionized and plasma protein binding data.
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    ABSTRACT: We developed an improved Lombardeo's method (J. Med. Chem., 2004) for prediction of VD(ss) in human. With ElogD substituted by logk(IAM), together with f(i (7.4)) (the fraction of compound ionized at pH 7.4) and logf(u) (logarithmic fraction of compound unbound in plasma), the predictive equation of f(ut) (the fraction of the compound unbound in tissues) for the 121 compounds was built, predictive VD(ss) was further obtained from the Øie-Tozer equation. Our model could be applicable to structurally diverse compounds, including acids, bases, neutrals, and ampholytes. Interior and exterior validation results indicated the model had a robust predictive ability. Compared to the Lombardeo's and Hollósy's (J. Med. Chem., 2006) methods, our model can be generally applicable with better predictive accuracy.
    European journal of medicinal chemistry 07/2009; 44(11):4455-60. · 3.27 Impact Factor
  • Article: Development of a chemically stable 10-hydroxycamptothecin nanosuspensions.
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    ABSTRACT: The purpose of this study was to prepare and characterize nanosuspensions loading the active lactone form of 10-hydroxycamptothecin (10-HCPT). Nanosuspensions were prepared in terms of microprecipitation-high-pressure homogenization method. As for the preparation processes, three important parameters, i.e. the agitation rate of stabilizer solution, homogenization pressure and cycle numbers, were investigated and optimized, and the optimal values were 1000 rpm, 1000 bar and 20 times, respectively. The particle size and zeta potential of the 10-HCPT-nanosuspensions were 131 nm and -25.5 mV. The particle morphology was determined by transmission electron microscopy and the 10-HCPT nanoparticles were baculine or trabecular in shape. The solid state of 10-HCPT in nanoparticles was analyzed using X-ray powder diffraction (XRD) and differential scanning calorimetry (DSC). The XRD and the DSC results both indicated that 10-HCPT was present as an amorphous state in the lyophilized powders for nanosuspension. The chemical stability tests demonstrated that near 90% lactone form of 10-HCPT was present in the nanosuspensions but it was easily transferred to the carboxylate form in the solution at pH 7.0-8.0. In vitro dissolution tests showed the dissolution rate of nanosuspensions, compared with the coarse suspensions, had been significantly increased.
    International journal of pharmaceutics 07/2009; 379(1):167-73. · 2.96 Impact Factor
  • Article: Structure-based prediction of the nonspecific binding of drugs to hepatic microsomes.
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    ABSTRACT: For the accurate prediction of in vivo hepatic clearance or drug-drug interaction potential through in vitro microsomal metabolic data, it is essential to evaluate the fraction unbound in hepatic microsomal incubation media. Here, a structure-based in silico predictive model of the nonspecific binding (fu(mic), fraction unbound in hepatic microsomes) for 86 drugs was successfully developed based on seven selected molecular descriptors. The R(2) of the predicted and observed log((1 - fu(mic))/fu(mic)) for the training set (n = 64) and test set (n = 22) were 0.82 and 0.85, respectively. The average fold error (AFE, calculated by fu(mic) rather than log((1 - fu(mic))/fu(mic))) of the in silico model was 1.33 (n = 86). The predictive capability of fu(mic) for neutral drugs compared well to that for basic compounds (R(2) = 0.82, AFE = 1.18 and fold error values were all below 2, except for felodipine and progesterone) in our model. This model appears to perform better for neutral compounds when compared to models previously published in the literature. Therefore, this in silico model may be used as an additional tool to estimate fu(mic) and for predicting in vivo hepatic clearance and inhibition potential from in vitro hepatic microsomal studies.
    The AAPS Journal 06/2009; 11(2):364-70. · 5.09 Impact Factor
  • Article: Separation and mechanism elucidation for six structure-like matrine-type alkaloids by micellar liquid chromatography.
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    ABSTRACT: A mixed micellar liquid chromatography (MLC) method, the mobile phase consisting of anionic surfactant SDS and nonionic surfactant Brij35, was firstly developed for the separation and determination of six structure-like matrine-type alkaloids, including matrine, oxymatrine, sophocarpine, oxysophocarpine, sophoridine, and oxysophoridine. The factors influencing the resolution of the six alkaloids were systematically investigated and optimized, including the micellar composition and concentration, column temperature, the type and amount of organic solvent, and the pH values in the mobile phases. Under the optimized separation conditions, the six matrine-type alkaloids could be easily isocratically eluted with a baseline separation within 22 min. Under the designated conditions (SDS concentration from 10 to 50 mM, Brij35 from 5 to 30 mM, pH 3 and 5% 1-propanol), the hydrophobic selectivity was negatively correlated with the concentration of Brij35 but not with SDS. The functional group selectivity of the carbonyl group, double bond, and diastereomers, all decreased with the increase in percentage of SDS in the mixed micellar phase, because the strong electrostatic force masks other molecular forces which can discriminate the retention of the analytes. Therefore, such a combination in surfactants of MLC is a powerful strategy to increase the selectivity by adjusting the balance among the various molecular interaction forces influencing analytes' retention. Finally, the developed method was successfully used to separate and determine the contents of main alkaloids in Sophora medicinal plants, S. flavescens Ait. In summary, the mixed MLC is a valuable approach to separate and determine the structure-like multi-component natural samples.
    Journal of Separation Science 06/2009; 32(12):2043-50. · 2.73 Impact Factor
  • Article: Characterization and In Vivo Evaluation of an Inclusion Complex of Oridonin and 2-hydroxypropyl-β-cyclodextrin
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    ABSTRACT: Oridonin, a diterpenoid, is a sparingly soluble compound and its aqueous solubility can't meet the requirement of clinical intravenous administration. This study was, accordingly, to prepare an inclusion complex of oridonin and 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) by lyophilization to improve its apparent solubility. The solubility enhancement of oridonin was evaluated by phase solubility method, and the phase solubility curve displayed a typical AL-type, indicating the formation of 1:1 inclusion complex. The formation of inclusion complex was confirmed by DSC, XRD, FTIR, and NMR, and thereby two possible inclusion modes were inferred. In vivo studies demonstrated that HP-β-CD had no significant effect on the plasma pharmacokinetic behaviors of oridonin following i.v. administration to rats, but the inclusion complex tended to decrease the distribution of oridonin in heart, spleen, and kidney and increase that in lung in mice, compared to that of free drug.
    09/2008; 34(6):632-641.
  • Article: Preparation and characterization of a submicron lipid emulsion of docetaxel: submicron lipid emulsion of docetaxel.
    Kun Gao, Jin Sun, Kai Liu, Xiaohong Liu, Zhonggui He
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    ABSTRACT: Docetaxel, a widely used anticancer agent, has sparingly low aqueous solubility, thus Tween 80 and ethanol need to be added into its formulation, probably resulting in the toxic effects. In this study, we aimed to utilize submicron lipid emulsions as a carrier of docetaxel to avoid these potential toxic vehicles. Preformulation study was performed for rational emulsions formulation design, including drug solubility, distribution between oil and water, and degradation kinetics. Supersaturated submicron lipid emulsion of docetaxel was prepared by temperature elevation method. Soya oil and Miglyol 812 can incorporate docetaxel up to 1.0% (drug to lipid ratio) and were used as the oil phase of emulsions. The optimal formulation of docetaxel is composed of 10% oil phase, 1.2% soybean lecithin, 0.3% Pluoronic F68, and 0.4 or 0.8 mg/mL docetaxel, with particle size in the nanometer range, entrapment efficiency more than 90%, and is physicochemically stable at 4 and 25 degrees C for 6 months. Animal studies showed that docetaxel emulsion has significantly higher area under the curve (AUC) and C(max) in rats compared to its micellar solution. The results suggested that the submicron lipid emulsion is a promising intravenous carrier for docetaxel in place of its present commercially available docetaxel micellar solution with potential toxic effects.
    Drug Development and Industrial Pharmacy 09/2008; 34(11):1227-37. · 1.49 Impact Factor
  • Article: Self-emulsifying drug delivery systems for improving oral absorption of ginkgo biloba extracts.
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    ABSTRACT: Self-emulsifying drug delivery systems (SEDDS) are mixtures of oils, surfactants, and cosurfactants, which are emulsified in aqueous media under conditions of gentle stirring and digestive motility that would be encountered in the gastrointestinal tract. We found that SEDDS could efficiently improve oral absorption of the sparingly soluble drugs by rapid self-emulsification and subsequently dispersion in the absorption sites. Ginkgo biloba extract (GBE) has become a widely used herbal remedy for increasing cognitive function in elderly people. The main purpose of our work is to prepare SEDDS for improving oral absorption of GBE. Pseudoternary phase diagrams were constructed to identify the efficient self-emulsification region, and particle size distributions of resultant emulsions were determined. The optimized formulation for bioavailability assessment consisted of 45% Tween 80-Cremophor EL35 (1:1, w/w), 10% 1, 2-propanediol, and 45% ethyl oleate. The mean droplet size distribution of the optimized SEDDS was approximately 100 nm when diluted with 500-fold volume of the distilled water. The in vitro dissolution rates of the active components of GBE SEDDS form were significantly faster than those of the GBE tablets. After single oral administration of 800 mg GBE as SEDDS or tablets to fasted dogs, the relative bioavailability of SEDDS for bilabolide and ginkgolide A and B was 162.1, 154.6, and 155.8% compared with the reference tablets, respectively. Our results suggested the potential and promising use of SEDDS for the efficient delivery of the sparingly soluble drugs or traditional Chinese medicines, such as GBE by oral administration.
    Drug Delivery 09/2008; 15(8):477-84. · 1.46 Impact Factor
  • Article: First-principle, structure-based prediction of hepatic metabolic clearance values in human.
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    ABSTRACT: The first-principle, quantitative structure-hepatic clearance relationship for 50 drugs was constructed based on selected molecular descriptors calculated by TSAR software. The R(2) of the predicted and observed hepatic clearance for the training set (n=36) and test set (n=13) were 0.85 and 0.73, respectively. The average fold error (AFE) of the in silico model was 1.28 (n=50). The prediction accuracy of in silico model was superior to in vitro hepatocytes' model in literature (n=50, AFE=2.55). It is attractive to predict human hepatic clearance based on molecular descriptors merely. The structure-based model can be used as an efficient tool in the rapid identification of hepatic clearance of new drug candidates in drug discovery.
    European journal of medicinal chemistry 08/2008; 44(4):1600-6. · 3.27 Impact Factor
  • Article: High-performance liquid chromatography for the determination of 3-n-butylphthalide in rat plasma by tandem quadrupole mass spectrometry: application to a pharmacokinetic study.
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    ABSTRACT: A rapid, sensitive and specific high performance liquid chromatography-electrospray ionization tandem quadrupole mass spectrometry (HPLC-MS/MS) method was developed and validated for the determination of 3-n-butylphthalide in rat plasma. Following protein precipitation with acetonitrile, 3-n-butylphthalide and glipizide (internal standard, I.S.) were separated using a gradient elution program on a C18 column and detected by mass spectrometry in positive ion mode with the multiple reaction monitoring (MRM) mode using the respective precursor to product ion combinations of m/z 191/145 for 3-n-butylphthalide and m/z 446/321 for glipizide, respectively. The total chromatographic running time was 2.5 min. The method was linear over the concentration range of 11.14-3480.00 ng/mL, using as little as 100 microL plasma. The lower limit of quantification (LLOQ) was 5.57 ng/mL. Finally, the method was successfully used to support a preclinical pharmacokinetic study of 3-n-butylphthalide in rats following intravenous administration.
    Journal of Chromatography B 08/2008; 870(1):135-9. · 2.89 Impact Factor
  • Article: Characterization and in vivo evaluation of an inclusion complex of oridonin and 2-hydroxypropyl-beta-cyclodextrin.
    [show abstract] [hide abstract]
    ABSTRACT: Oridonin, a diterpenoid, is a sparingly soluble compound and its aqueous solubility can't meet the requirement of clinical intravenous administration. This study was, accordingly, to prepare an inclusion complex of oridonin and 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CD) by lyophilization to improve its apparent solubility. The solubility enhancement of oridonin was evaluated by phase solubility method, and the phase solubility curve displayed a typical A(L)-type, indicating the formation of 1:1 inclusion complex. The formation of inclusion complex was confirmed by DSC, XRD, FTIR, and NMR, and thereby two possible inclusion modes were inferred. In vivo studies demonstrated that HP-beta-CD had no significant effect on the plasma pharmacokinetic behaviors of oridonin following i.v. administration to rats, but the inclusion complex tended to decrease the distribution of oridonin in heart, spleen, and kidney and increase that in lung in mice, compared to that of free drug.
    Drug Development and Industrial Pharmacy 07/2008; 34(6):632-41. · 1.49 Impact Factor
  • Article: Characterization of microemulsion liquid chromatography systems by solvation parameter model and comparison with other physicochemical and biological processes.
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    ABSTRACT: The solvation parameter model has been applied to characterize four microemulsion liquid chromatography (MELC) systems and two micellar liquid chromatography (MLC) systems, and utilized to compare the above systems with other physicochemical and biological processes in this study. The microemulsion mobile phases were composed of sodium dodecyl sulfate (SDS), polyoxyethylene (23) lauryl ether (Brij 35), butanol, heptane and phosphate buffer (pH 7.0) at the designated ratios. The results showed the main difference between the concerned MELC and MLC systems was the decrease of hydrogen-bond basicity of stationary phase with the addition of heptane in microemulsion. Principal component analysis with normalized coefficients can provide consistent results involving the similarities among various systems with that obtained by distance parameter d. Except for some proven similarities of chromatographic systems to octanol-water partition coefficients (logP) and human skin permeation (logK(p)), a microemulsion HPLC system, the mobile phase being 3.3% SDS-6.6% butanol-1.6% heptane-88.5% buffer, was found very similar to drug penetration across blood-brain barrier and its predictive capability for this biological process was originally evaluated in this study.
    Journal of Chromatography 10/2007; 1164(1-2):129-38. · 4.53 Impact Factor