Z M Du

Shenyang Pharmaceutical University, Feng-t’ien, Liaoning, China

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Publications (4)0 Total impact

  • X Y Chen · Y Luan · D F Zhong · Z M Du
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    ABSTRACT: To develop a sensitive and specific LC/MS/MS method for determination of amlodipine in human plasma. Amlodipine and internal standard 4'-hydroxypropafenone were extracted from plasma using liquid-liquid extraction, then separated on a Zorbax C8 column. The mobile phase consisted of acetonitrile-water-formic acid (75:35:1), at a flow-rate of 0.4 mL.min-1. A Finnigan TSQ tandem mass spectrometer equipped with electrospray ionization source was used as detector and was operated in the positive ion mode. Selected reaction monitoring (SRM) using the precursor-->product ion combinations of m/z 409-->238 and m/z 358-->116 was used to quantify amlodipine and internal standard, respectively. The linear calibration curves were obtained in the concentration range of 0.4-16.0 ng.mL-1. The limit of quantification was 0.4 ng.mL-1. Each plasma sample was chromatographed within 3.7 min. The method was successfully used in several pharmacokinetic studies for amlodipine. More than 1,500 plasma samples were assayed within two weeks. The method is proved to be suitable for clinical investigation of amlodipine pharmacokinetics, which offers advantages of specificity, speed, and greater sensitivity over the previously reported methods.
    No preview · Article · Feb 2001 · Yao xue xue bao = Acta pharmaceutica Sinica
  • Z M Du · H H Huang · X Y Chen · D F Zhong
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    ABSTRACT: To investigate the hydroxylation process of benproperine in humans. After an oral administration of 60 mg benproperine to ten healthy male volunteers, urine samples collected within 0-24 h were extracted by solid phase extraction and analyzed by liquid chromatography-ion trap mass spectrometry. A microbial transformation of benproperine combined with semi-preparative HPLC was used to get two reference substances of the hydroxylated metabolites, and their structures were then elucidated by NMR. Furthermore, the structures of conjugated metabolites were speculated based on their characteristics in MS fragmentation. Five hydroxylated metabolites of benproperine and some of their conjugates with endogenous glucuronic acid or sulfuric acid were found in urine of volunteers after the dose. The structures of two metabolites were identified as 4"-hydroxybenproperine and 4"'-hydroxybenproperine by comparison of HPLC retention times and mass spectra with those of authentics obtained from the microbial transformation. Hydroxylation of benproperine occurs preferentially at para-position of the alkoxyl group in the aromatic ring. The hydroxylated metabolites of benproperine in human urine mainly exist as their glucuronic acid or sulfuric acid conjugates.
    No preview · Article · Jan 2001 · Yao xue xue bao = Acta pharmaceutica Sinica
  • H.-H. Hua · H.-X. Cui · D.-F. Zhong · Z.-M. Du
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    ABSTRACT: Studies on biotransformation of benproperine by Cunninghamella blakesleana AS 3.153 were conducted. The observed transformation products were metabolites of mono-hydroxylation (approx. 65%), di-hydroxylation and sulfate conjugation of mono-hydroxylated derivatives of benproperine by LC/MSn data. Compared with data of metabolites in urine of healthy male volunteers, similarities were found between microorganism and humans in the transformation of benproperine. The transformation organism produced phase I and a part of phase II metabolites in humans. Influences of the mono-hydroxylation were investigated, and the optimized conditions were pH 6.5, 0.05% of substrate concentration, and 72 h of incubation. Semi-preparative HPLC was used to isolate two major transformation products, and their structures were then identified as 4-hydroxybenproperine and 4′-hydroxybenproperine by NMR, respectively. Microbial model of transformation is shown to be a suitable in vitro model for benproperine metabolism.
    No preview · Article · Jan 2001 · Chinese Journal of Pharmacology and Toxicology
  • Z M Du · D F Zhong · Y Kang · X Y Chen
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    ABSTRACT: To investigate the enantioselective pharmacokinetic process of benproperine in healthy volunteers. An enantiospecific HPLC method was developed and used to determine the plasma concentrations of each enantiomer. Six healthy Chinese male volunteers received an oral dose of 60 mg (+/-)-benproperine. The ratios of the enantiomers in plasma samples were measured on a chiral AGP column. The plasma concentration of each enantiomer was then calculated using the ratios of enantiomers and total concentration of the two enantiomers previously measured. The plasma levels of (-)-(S)-benproperine were always significantly higher than those of its antipode in six volunteers. The mean AUC0-t and Cmax values for (-)-(S)-benproperine were 2.18 and 2.12 times higher than those of (+)-(R)-benproperine. There was no significant difference between the T1/2 for both enantiomers, tested by paired t test (P > 0.05). Half an hour after administration of benproperine, the S/R ratio in plasma samples was as high as 3.8, and in 2 hours it drastically decreased to about 2.2, then kept on till 24 hours. Benproperine showed significant enantioselective pharmacokinetics in the human after an oral dose of the racemate.
    No preview · Article · Dec 2000 · Yao xue xue bao = Acta pharmaceutica Sinica