Zeneng Cheng

Central South University, Ch’ang-sha-shih, Hunan, China

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Publications (22)57.05 Total impact

  • Feifan Xie, Shan Ji, Zeneng Cheng
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    ABSTRACT: The present study examined the agreement between in vitro dissolution f2 similarity and in vivo bioequivalence criteria for BCS class II drugs. Dissolution test profiles were generated using the First-order model with varied dissolution parameters around the standard values of a reference profile. The in vivo curves were derived from in vitro dissolution profiles with the drug's pharmacokinetics parameters by numerical convolution method. The Cmax, Tmax, AUC0-t and AUC0-∞ obtained from in vivo test and reference concentration-time curves were compared, and the CmaxR (Cmax ratio), TmaxDif (Tmax difference), AUC0-tR (AUC0-t ratio) and AUC0-∞R (AUC0-∞ ratio) were determined. The relationships between CmaxR, AUC0-tR, AUC0-∞R, f2 and the First-order model parameters demonstrated that the Similarity Region 1 enclosed by the f2 contour line labeled 50 was completely within the Bioequivalence Region enclosed by the contour lines labeled 0.80 and 1.20 of AUC0-tR, AUC0-∞R, and CmaxR, and the Similarity Region 2 enclosed by the f2 contour line labeled 35 was nearly overlapped with the Bioequivalence Region, but did not exactly match. The results indicate that the public standard for in vitro dissolution f2 similarity criterion (f2⩾50) is probably slightly conservative and may be widened to an appropriate lower critical value.
    European journal of pharmaceutical sciences: official journal of the European Federation for Pharmaceutical Sciences 10/2014; · 2.61 Impact Factor
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    ABSTRACT: Defective autophagy is implicated in the pathogenesis of nonalcoholic fatty liver diseases (NAFLD) through poorly defined mechanisms. Cardiolipin is a mitochondrial phospholipid required for bioenergetics and mitophagy from yeast to mammals. Here, we investigated a role for ALCAT1 in the development of NAFLD. ALCAT1 is a lysocardiolipin acyltransferase that catalyzes pathological cardiolipin remodeling in several aging-related diseases. We show that the onset of diet-induced NAFLD caused autophagic arrest in hepatocytes, leading to oxidative stress, mitochondrial dysfunction, and insulin resistance. In contrast, targeted deletion of ALCAT1 in mice prevented the onset of NAFLD. ALCAT1 deficiency also restored mitophagy, mitochondrial architecture, mtDNA fidelity, and oxidative phosphorylation. In support for a causative role of the enzyme in mitochondrial etiology of the disease, hepatic ALCAT1 expression was significantly up-regulated in mouse models of NAFLD. Accordingly, forced expression of ALCAT1 in primary hepatocytes led to multiple defects that are highly reminiscent of NAFLD, including hepatosteatosis, defective autophagy, and mitochondrial dysfunction, linking pathological cardiolipin remodeling by ALCAT1 to the pathogenesis of NAFLD. (Hepatology 2014)
    Hepatology 09/2014; · 12.00 Impact Factor
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    Feifan Xie, Zeneng Cheng, Hang Cheng, Peng Yu
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    ABSTRACT: A simple, sensitive and cost-effective assay based on reversed phase high performance liquid chromatography (RP-HPLC) with isocratic mode for simultaneous determination of bendamustine (BM) and its active metabolite, gamma-hydroxy-bendamustine (γ-OH-BM) in human plasma and urine was developed and validated. Sample preparation involved protein precipitation by 10% perchloric acid-methanol solution. The peaks were recorded by using fluorescence detector (excitation wavelength 328nm and emission wavelength 420nm). The calibration curves were linear over concentration ranges of 8.192-10,000ngmL(-1) and 5-1000ngmL(-1) for BM in human plasma and urine as well as 10-1000ngmL(-1) and 5-1000ngmL(-1) for γ-OH-BM in human plasma and urine, respectively. Intra- and inter-run precisions of BM and γ-OH-BM were less than 15% and the bias were within ±15% for both plasma and urine. This validated method was successfully applied to a pharmacokinetic study enrolling 10 Chinese patients with indolent B-cell non-Hodgkin lymphoma and chronic lymphocytic leukemia administered a single intravenous infusion of 100mgm(2) bendamustine hydrochloride.
    Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 04/2014; 960C:98-104. · 2.78 Impact Factor
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    ABSTRACT: Benfotiamine is a lipid-soluble thiamine precursor which can transform to thiamine in vivo and subsequently be metabolized to thiamine monophosphate (TMP) and thiamine diphosphate (TDP). This study investigated the pharmacokinetic profiles of thiamine and its phosphorylated metabolites after single- and multiple-dose administration of benfotiamine in healthy Chinese volunteers, and assessed the bioavailability of orally benfotiamine administration compared to thiamine hydrochloride. In addition, concentration of hippuric acid in urine which is produced in the transformation process of benfotiamine was determined. The results showed that thiamine and its phosphorylated metabolites exhibited different pharmacokinetic characteristics in plasma, blood and erythrocyte, and one-compartment model provided the best fit for pharmacokinetic profiles of thiamine. The transformation process of benfotiamine to thiamine produced large amount of hippuric acid. No accumulation of hippuric acid was observed after multiple-dose of benfotiamine. Compared to thiamine hydrochloride, the bioavailability of thiamine in plasma and TDP in erythrocyte after oral administration of benfotiamine were 1147.3 ± 490.3% and 195.8 ± 33.8%, respectively. The absorption rate and extent of benfotiamine systemic availability of thiamine were significantly increased indicating higher bioavailability of thiamine from oral dose of benfotiamine compared to oral dose of thiamine hydrochloride.
    The Journal of Clinical Pharmacology 01/2014; · 2.84 Impact Factor
  • Feifan Xie, Zeneng Cheng, Hang Cheng, Peng Yu
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    ABSTRACT: A simple, sensitive and cost-effective assay based on reversed phase high performance liquid chromatography (RP-HPLC) with isocratic mode for simultaneous determination of bendamustine (BM) and its active metabolite, gamma-hydroxy-bendamustine (γ-OH-BM) in human plasma and urine was developed and validated. Sample preparation involved protein precipitation by 10% perchloric acid-methanol solution. The peaks were recorded by using fluorescence detector (excitation wavelength 328 nm and emission wavelength 420 nm). The calibration curves were linear over concentration ranges of 8.192-10,000 ng·mL−1 and 5-1000 ng·mL−1 for BM in human plasma and urine as well as 10-1000 ng·mL−1 and 5-1000 ng·mL−1 for γ-OH-BM in human plasma and urine, respectively. Intra- and inter-run precisions of BM and γ-OH-BM were less than 15% and the bias were within ±15% for both plasma and urine. This validated method was successfully applied to a pharmacokinetic study enrolling 10 Chinese patients with indolent B-cell non-Hodgkin lymphoma and chronic lymphocytic leukemia administered a single intravenous infusion of 100 mg·m2 bendamustine hydrochloride.
    Journal of Chromatography B. 01/2014;
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    ABSTRACT: Simotinib is a novel epidermal growth factor receptor tyrosine kinase inhibitor. This study presented a sensitive and specific liquid chromatography-electrospray ionization-mass spectrometry method using erlotinib as internal standard for the determination of simotinib in human plasma. The method involved a simple liquid-liquid extraction using diethyl ether. The analytes were separated with isocratic gradient elution on an Agilent TC-C18 column (4.6×150mm, 5μm). Mass spectrometric detector equipped with electrospray ionization source was carried out in the mode of multiple reaction monitoring (MRM). The monitored transitions were m/z 501.2→182.1 for simotinib and m/z 394.4→278.1 for erlotinib. The calibration curve of simotinib was established over the range of 2.058-3000μgL(-1) (r(2)=0.9924). The intra- and inter-day precisions were all less than 10%, and all the biases were not more than 7%. This validated method was then successfully applied to a pharmacokinetic study involving twelve healthy Chinese volunteers. The mean Cmax and Tmax for simotinib were 254.79±98.30 μgL(-1) and 1.71±0.48 h, respectively. Plasma concentrations declined with a t1/2 of 5.37±2.32 h. AUC0-t and AUC0→∞ values obtained were 1262.59±501.41 μgL(-1)h and 1329.95±517.42 μgL(-1)h, respectively.
    Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 12/2013; 947-948C:168-172. · 2.78 Impact Factor
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    ABSTRACT: A rapid, specific and sensitive HPLC–MS/MS method was developed and validated for the determination of 20(S)-protopanaxadiol (PPD) in human plasma. PPD and the internal standard PD were extracted from plasma by liquid–liquid extraction with cyclohexane–methylene dichloride (2:1, v/v). The separation was performed on a HyPURIYTY C18 column using methanol–5 mM ammonium formate (90:10, v/v) as mobile phase at a flow rate of 0.35 mL/min. Mass spectrometric detection was carried out by electrospray ionization (ESI) in the positive ion mode using multiple reaction monitoring (MRM). The monitored transitions were m/z 425.4→217.2 for PPD and at m/z 461.4→425.5 for PD. The method was linear over the range 0.512–100 ng/mL with a lower limit of quantification (LLOQ) of 0.512 ng/mL. The mean extraction recovery of PPD was greater than 78.2% and no significant matrix effect was detected. The intra- and inter-day precisions were less than 10% and the biases below 4% for PPD. The validated method was applied to a three-level single-dose clinical pharmacokinetics study of 12 healthy Chinese volunteers and the main pharmacokinetic parameters of PPD were obtained.
    Acta Pharmaceutica Sinica B. 12/2013;
  • Xi Luo, Ningfang Cai, Zeneng Cheng
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    ABSTRACT: A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of uric acid in human plasma was developed and validated. Separation was achieved on a C18 column by the mobile phase of 30% water (containing 0.5% formic acid) and 70% methanol. Quantification was done using a multiple reaction monitoring (MRM) mode to monitor the precursor-to-product ion transitions of m/z 169.1 → m/z 141.1 for uric acid and m/z 171 → m/z 143 for 1,3-(15)N uric acid (IS) at a positive ionization mode. The calibration curve was established over the range of 0.4096 - 100 mg/L, and the correlation coefficient was better than 0.99. The intra-day and inter-day relative standard deviations were less than 5.1%. The accuracy determined at three concentrations ranged between 92.7 and 102.3%. This method was successfully applied to an efficacy study of intravenous recombinant urate oxidase produced by Escherichia coli in a clinical phase I study.
    Analytical Sciences 01/2013; 29(7):709-713. · 1.57 Impact Factor
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    ABSTRACT: Oxidative stress causes mitochondrial dysfunction and heart failure through unknown mechanisms. Cardiolipin (CL), a mitochondrial membrane phospholipid required for oxidative phosphorylation, plays a pivotal role in cardiac function. The onset of age-related heart diseases is characterized by aberrant CL acyl composition that is highly sensitive to oxidative damage, leading to CL peroxidation and mitochondrial dysfunction. Here we report a key role of ALCAT1, a lysocardiolipin acyltransferase that catalyzes the synthesis of CL with a high peroxidation index, in mitochondrial dysfunction associated with hypertrophic cardiomyopathy. We show that ALCAT1 expression was potently upregulated by the onset of hyperthyroid cardiomyopathy, leading to oxidative stress and mitochondrial dysfunction. Accordingly, overexpression of ALCAT1 in H9c2 cardiac cells caused severe oxidative stress, lipid peroxidation, and mitochondrial DNA (mtDNA) depletion. Conversely, ablation of ALCAT1 prevented the onset of T4-induced cardiomyopathy and cardiac dysfunction. ALCAT1 deficiency also mitigated oxidative stress, insulin resistance, and mitochondrial dysfunction by improving mitochondrial quality control through upregulation of PINK1, a mitochondrial GTPase required for mitochondrial autophagy. Together, these findings implicate a key role of ALCAT1 as the missing link between oxidative stress and mitochondrial dysfunction in the etiology of age-related heart diseases.
    Molecular and Cellular Biology 09/2012; 32(21):4493-504. · 5.04 Impact Factor
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    ABSTRACT: In order to increase the intestinal permeability of valsartan, 14 esters and peptide derivatives of valsartan were chemically synthesized and their absorption characteristics were described. All derivatives were stable and could be better absorbed into the small intestine than valsartan. There are two barriers for the absorption of valsartan derivatives. The elongated half-life (t(1/2)) and stable blood concentrations for compound 4 due to the hydrolysis of the ester group in the second barrier were demonstrated in pharmacokinetic experiments. Furthermore, compound 4 also displayed modest anti-hypertension activity in vivo, which makes structural modification of valsartan, especially for the purpose of improvement of its intestinal permeability, valuable for further studies.
    Archiv der Pharmazie 01/2012; 345(5):393-400. · 1.54 Impact Factor
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    ABSTRACT: Nifeviroc is a novel CCR5 antagonist used for the treatment of HIV type-1 infection. A LC-ESI-MS/MS method for the determination of nifeviroc in human plasma was developed and validated. The calibration curve (r(2)=0.9993) of nifeviroc was established at the range of 1.924-2935 μg L(-1). The intra- and inter-day precisions (RSD%) were all less than 7%, and the accuracies at three concentration levels were all within 100 ± 5%. This validated method was then successfully applied to a pharmacokinetic study in health Chinese volunteers.
    Journal of pharmaceutical and biomedical analysis 11/2011; 56(3):637-40. · 2.45 Impact Factor
  • Xiaoai He, Xi Luo, Zhi Liu, Gaoyun Hu, Zeneng Cheng
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    ABSTRACT: Identification of cytochrome P450 isoforms (CYPs) involved in flourofenidone (5-methyl-1-(3-fluorophenyl)-2-[1H]-pyridone, AKF-PD) 5-methylhydroxylation was carried out using human liver microsomes and cDNA-expressed human CYPs (supersomes). The experiments were performed in the following in vitro models: (A) a study of AKF-PD metabolism in liver microsomes: (a) correlations study between the rate of AKF-PD 5-methylhydroxylation and activity of CYPs; (b) the effect of specific CYPs inhibitors on the rate of AKF-PD 5-methylhydroxylation; (B) AKF-PD biotransformation by cDNA-expressed human CYPs (1A2, 2D6, 2C9, 2C19, 2E1, 3A4). In human liver microsomes, the formation of AKF-PD 5-methylhydroxylation metabolite significantly correlated with the caffeine N3-demethylase (CYP1A2), chlorzoxazone 6-hydroxylase (CYP2E1), midazolam 1'- hydroxylase (CYP3A4), tolbutamide 4-hydroxylase (CYP2C9), and debrisoquin 4-hydroxylase (CYP2D6) activities. The production of AKF-PD 5-methylhydroxylation metabolite was completely inhibited by a-naphthoflavone (a CYP1A2 inhibitor) with the IC50 value of 0.12 μM in human liver microsomes. The cDNA-expressed human CYPs generated different amounts of AKF-PD 5-methylhydroxylation metabolites, but the preference of CYP isoforms to catalyze AKF-PD metabolism was as follows: 2D6 > 2C19 > 1A2 > 2E1 > 2C9 > 3A4. The results demonstrated that CYP1A2 is the main isoform catalyzing AKF-PD 5-methylhydroxylation while CYP3A4, CYP2C9, CYP2E1, CYP2C19, and CYP2D6 are engaged to a lesser degree. Potential drug-drug interactions involving CYP1A2 may be noticed when AKF-PD is used combined with CYP1A2 inducers or inhibitors.
    Xenobiotica 06/2011; 41(10):844-50. · 1.98 Impact Factor
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    ABSTRACT: A sensitive, specific and rapid high performance liquid chromatography–atmospheric pressure chemical ionization source-tandem mass spectrometry (LC-APCI-MS-MS) method for the determination of pilocarpine in human plasma was developed and validated. The method is based on liquid–liquid extraction, followed by a reversed-phase liquid chromatographic separation, and detected by means of tandem mass spectrometry. The linear calibration curve covered a concentration range of 2–500μgL−1. The intra- and inter-day precisions for pilocarpine were <10% and the accuracies were between 90 and 110%. The method was applied successfully to a pharmacokinetic study involving 20 healthy Chinese male volunteers after oral administration of 6mg pilocarpine. KeywordsColumn liquid chromatography–LC-APCI-MS-MS–Pilocarpine–Human plasma–Pharmacokinetic study
    Chromatographia 05/2011; 73(9):921-927. · 1.44 Impact Factor
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    ABSTRACT: A sensitive, specific, and rapid high-performance liquid chromatography-atmospheric pressure chemical ionization source-tandem mass spectrometry (HPLC-APCI-MS/MS) method for the determination of glucosamine in human plasma was developed and validated. Plasma samples were processed by protein precipitation with dehydrated ethanol, and the chromatographic separation was performed on an Agilent XDB-C 18 column with a mobile phase of methanol—0.2% formic acid solution (70 : 30, v/v). Mass spectrometric quantification was carried out in the multiple reaction monitoring (MRM) mode, monitoring ion transitions of m/z 180.1 to m/z 162.1 with collision energy (CE) of 2 eV for glucosamine and m/z 181.1 to m/z 163.1 with CE of 2 eV for the internal standard (IS) in positive ion mode. The linear calibration curves covered a concentration range of 53.27– 3409 ng/mL with a lower limit of quantification (LLOQ) of 53.27 ng/mL. The extraction recovery of glucosamine was greater than 101.7%. The intra-and interday precisions for glucosamine were less than 10%, and the accuracies were between 93.7% and 102.6%, determined from quality control (QC) samples of three representative concentrations. The method has been successfully applied to determining the plasma concentration of glucosamine in a clinical pharmacokinetic study involving 20 healthy Chinese male volunteers.
    01/2011; 7.
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    ABSTRACT: A sensitive, specific, and rapid liquid chromatography–electrospray ionization–tandem mass spectrometry (LC–ESI–MS–MS) method was developed for determination of revaprazan in human plasma. Plasma samples were simply treated with methanol to precipitate, and then isolated supernatants were directly injected into the LC–ESI–MS–MS system. A Thermo Hypurity C18 column (150 × 2.1 mm, 5 μm) with mobile phase of methanol–water (70:30, v/v) containing 0.05% formic acid was used for chromatographic separation. Mass-spectrometric quantification was carried out in multiple reaction monitoring (MRM) mode, monitoring the m/z transitions 363.1 → 245.1 for revaprazan and 531.2 → 489.2 for ketoconazole (internal standard, IS) in positive ion mode. The linear calibration curves covered a concentration range of 2–1,000 μg L−1. The intra- and interday precisions (percentage relative standard deviation, RSD%) for revaprazan at three quality control levels were all
    Chromatographia 01/2011; 73(7):667-672. · 1.44 Impact Factor
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    ABSTRACT: The objective of this work was to establish a sensitive, simple, accurate, and reliable LC–APCI-MS–MS method for analysis of zidovudine in human plasma. Plasma samples were processed by protein precipitation with perchloric acid solution. Separation on a 250mm×4.6mm, 5μm particle, C18 column was achieved by use of methanol–water 65:35 (v/v) containing 0.2% formic acid as mobile phase. Mass spectrometric quantification was performed in positive-ion multiple reaction monitoring (MRM) mode, by monitoring the m/z transitions 268.1→127.0 for zidovudine and m/z 248.1→121.0 for tinidazole (internal standard). The calibration plot was linear in the concentration range 1.638–6250μgL−1, and the lower limit of quantification (LLOQ) was 1.638μgL−1. Intra-day and inter-day precision (as RSD) for zidovudine at four quality-control levels was less than 15%, and accuracy was between 95.1 and 114.2%. The method enables simple, sensitive, and accurate analysis of zidovudine in human plasma, and was successfully used in a bioequivalence study of 48 healthy Chinese volunteers. KeywordsColumn liquid chromatography-LC–APCI-MS–MS-Zidovudine-Human plasma-Bioequivalence study
    Chromatographia 01/2010; 72(1):151-155. · 1.44 Impact Factor
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    ABSTRACT: A liquid chromatographic method for the simultaneous determination of 6β-hydroxycortisol and 6β-hydroxycortisone using dexamethasone as internal standard in human urine is described. Separation was achieved on a reversed-phase C18 column by a gradient elution of acetonitrile and water containing 0.1% formic acid. 6β-Hydroxycortisol and 6β-hydroxycortisone were monitored by UV absorption at 244nm. The lower limits of quantitation were 5ngmL−1 for both analytes. The intra-day and inter-day relative standard deviations were less than 7.4%. Accuracy determined at three concentrations ranged between 92.16 and 109.77%. The sensitivity, specificity and accuracy of this method were demonstrated to be satisfactory for measuring both metabolites in human urine.
    Chromatographia 01/2009; 70(7):1215-1219. · 1.44 Impact Factor
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    ABSTRACT: A simple, rapid, and reproducible isocratic reverse-phase HPLC method was developed to simultaneously determine AKF-PD and its two oxidized metabolites in rat plasma. 5-Carboxyl-1-phenyl-2-(1H)-pyridone and phenacetin were used as internal standards to ensure the precision and accuracy of the method. The analytes were separated on a C18 reversed-phase column with methanol—phosphate buffer (20 mM, pH 2.5) as mobile phase. The limits of detection for AKF-PD and its two oxidized metabolites was 0.1 μg mL−1. The method is applicable for the pharmacokinetic studies of AKF-PD and its metabolites in rats.
    Chromatographia 01/2008; 67(11):947-950. · 1.44 Impact Factor
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    ABSTRACT: An HPLC-UV method was developed and validated for the determination of AKF-PD in whole blood of rat. Phenacetin was chosen as the internal standard, and the separation was achieved on a C18 column with methanol and 0.02 M phosphate buffer (pH 3.2) as mobile phase. The obtained calibration graphs were linear (r = 0.9999, n = 9) in the range of 0.203-52.0 microg ml(-1). The low limit of quantitation was 0.203 microg ml(-1). This method can be used to study the pharmacokinetics of AKF-PD in rat.
    Journal of Chromatography B 05/2006; 833(2):257-9. · 2.49 Impact Factor
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    ABSTRACT: This study describes an high-performance liquid chromatographic (HPLC)-UV method for the simultaneous determination of 6beta-hydroxycortisol (6beta-OHF) and cortisol (F) in human urine and plasma. The within-day relative standard deviation of the three concentrations for both analytes was less than 6.2%. Accuracy determined at three concentrations ranged between 95 and 107%. The extraction recoveries were 64.1+/-4.3 and 88.1+/-2.4% at three concentrations for 6beta-OHF and F in urine, respectively. The extraction recoveries were 88.7+/-1.4% at three concentrations for F in plasma. This is the first HPLC method that can simultaneously determine 6beta-OHF and F in human urine and plasma and is suitable for routine assessment of the CYP3A activity expressed as 6beta-hydroxylation clearance.
    Journal of Chromatography B 12/2005; 826(1-2):238-43. · 2.49 Impact Factor

Publication Stats

57 Citations
57.05 Total Impact Points

Institutions

  • 2005–2014
    • Central South University
      • School of Pharmaceutical Sciences
      Ch’ang-sha-shih, Hunan, China
  • 2012
    • Pennsylvania State University
      • Department of Cellular and Molecular Physiology
      University Park, Maryland, United States