Lijuan Jing

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

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Publications (5)11.22 Total impact

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    ABSTRACT: The chiral inversion and pharmacokinetics of two enantiomers of trantinterol, a new β2 agonist, were studied in rats dosed (+)- or (-)-trantinterol separately. Plasma concentrations of (+)- and (-)-trantinterol were measured by chiral stationary phase liquid chromatography tandem mass spectroscopy (LC-MS/MS). The apparent inversion ratio was calculated as the ratio of AUC0-t of (-)-trantinterol or (+)-trantinterol inverted from their antipodes to the sum of the AUC0-t of (-)- and (+)-trantinterol. Following single intravenous administration, both given enantiomers declined in similar plasma concentrations, suggesting that the two enantiomers have approximately the same disposition kinetics by the route of intravenous administration. However, after single oral administration, plasma concentrations of uninverted (-)-trantinterol at many timepoints were significantly higher than those of uninverted (+)-trantinterol, suggesting that the two enantiomers undergo apparently different absorption or metabolism after oral administration. Significant bidirectional chiral inversion occurred after intravenous and oral administration of (+)- or (-)-trantinterol. After dosing with optically pure enantiomer, the concentration of the administered enantiomer predominated in vivo. The AUC0-36 of (+)-trantinterol after intravenous and oral dosing of (-)-trantinterol were 16.6 ± 5.2 and 33.3 ± 16%, respectively of those of total [(+) + (-)] trantinterol. The AUC0-36 of (-)-trantinterol after intravenous and oral dosing of (+)-trantinterol were 19.6 ± 8.8 and 37.9 ± 4.5%, respectively, of those of total [(-) + (+)] trantinterol. After intravenous administration of (+)- and (-)-trantinterol the chiral inversion ratios of the two enantiomers were not significantly different and similar results were found for oral administration. The extent of chiral inversion after intravenous administration was apparently lower, indicating that the bidirectional chiral inversion was not only systemic but also presystemic. Chirality 00:000-000, 2013.© 2013 Wiley Periodicals, Inc.
    Chirality 12/2013; 25(12). DOI:10.1002/chir.22236 · 1.72 Impact Factor
  • Kunjie Li · Feng Qin · Lijuan Jing · Famei Li · Xingjie Guo
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    ABSTRACT: Trantinterol is a novel β(2)-adrenoceptor agonist used for the treatment of asthma. The aim of this study is to identify the metabolites of trantinterol using liquid chromatography tandem mass spectrometry (LC-MS/MS), to isolate the main metabolites, and confirm their structures by nuclear magnetic resonance (NMR). Urine, feces, bile, and blood samples of rats were obtained and analyzed. Reference standards of six metabolites were achieved with the combination of chemical synthesis, microbial transformation, and the model systems of rats. Moreover, in order to investigate the phase I metabolism of trantinterol in humans and to study the species differences between rats and humans, incubations with liver microsomes were performed. The biotransformation by a microbial model Cunninghamella blakesleana AS 3.970 was also studied. A total of 18 metabolites were identified in vivo and in vitro together, 13 of which were newly detected. Three phase I metabolites were detected in vivo and in vitro as well as in the microbial model, including the arylhydroxylamine (M1), the tert-butyl hydroxylated trantinterol (M2) and the 1-carbonyltrantinterol (M3). Another important pathway in rats is glutathione conjugation and further catabolism and oxidation to form consecutive derivatives (M4 through M10). Other metabolites include glucuronide, glucoside, and sulfate conjugates. The results of in vitro experiments indicate no species difference exists among rats, humans, and C. blakesleana AS 3.970 on the phase I metabolism of trantinterol. Our study provided the most comprehensive picture for trantinterol in vivo and in vitro metabolism to this day, and may predict its metabolism in humans.
    Analytical and Bioanalytical Chemistry 01/2013; 405(8). DOI:10.1007/s00216-012-6652-9 · 3.58 Impact Factor
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    ABSTRACT: A simple, sensitive, and rapid method for determination of L-trantinterol in rat plasma was developed for the first time by using LC coupled to MS/MS based on chiral stationary phase. A baseline separation of the enantiomers of trantinterol was achieved on a Chirobiotic V column, using a mixture of acetonitrile-methanol-ammonia-acetic acid (80:20:0.01:0.02, v/v/v/v) as the mobile phase. The detection was performed on a triple-quadrupole tandem mass spectrometer by multiple reaction monitoring mode via ESI. The calibration curve was linear in concentration range from 0.270 to 108 ng/mL in plasma with the lower limit of quantification of 0.270 ng/mL. The intra- and interday precision (relative standard deviation) values were within 10.9% and the accuracy (relative error) was from 2.6 to 9.2% at all quality control levels. The method has been successfully applied to a study of L-trantinterol pharmacokinetics in rats.
    Journal of Separation Science 10/2012; 35(20):2678-84. DOI:10.1002/jssc.201200332 · 2.59 Impact Factor
  • Xintao Wang · Feng Qin · Lijuan Jing · Qiang Zhu · Famei Li · Zhili Xiong
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    ABSTRACT: A sensitive, rapid and selective ultra-performance liquid chromatography-tandem mass spectrometric (UPLC-MS/MS) method was developed for the determination and pharmacokinetic study of domperidone in human plasma. Diphenhydramine was used as the internal standard. Plasma sample pretreatment involved a one-step liquid-liquid extraction with a mixture of diethyl ether-dichloromethane (3:2, v/v). The analysis was carried out on an Acquity UPLC(TM) BEH C(18) column. The mobile phase consisted of methanol-water containing 10 mmol/L ammonium acetate and 0.5% (v/v) formic acid (60:40, v/v). The detection was performed on a triple quadrupole tandem mass spectrometer in multiple reaction monitoring mode via electrospray ionizationsource with positive mode. Each plasma sample was chromatographed within 2.1 min. The standard curves for domperidone were linear (r(2)  ≥ 0.99) over the concentration range of 0.030-31.5 ng/mL with a lower limit of quantification of 0.030 ng/mL. The intra- and inter-day precision (relative standard deviation) values were not higher than 13% and accuracy (relative error) was from -7.6 to 1.2% at three quality control levels. The method herein described was superior to previous methods and was successfully applied to the pharmacokinetic study of domperidone in healthy Chinese volunteers after oral administration. Copyright © 2012 John Wiley & Sons, Ltd.
    Biomedical Chromatography 08/2012; 27(3). DOI:10.1002/bmc.2801 · 1.66 Impact Factor
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    Feng Qin · Dan Wang · Shuyan Yang · Lijuan Jing · Zhili Xiong · Famei Li
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    ABSTRACT: A rapid, selective and sensitive high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was developed to determine lisinopril in human plasma. Sample pretreatment involved a one-step protein precipitation with methanol of 0.1 mL plasma. Analysis was performed on an Inertsil ODS-3 column (2.1 × 50 mm i.d., 3 µm) with mobile phase consisting of methanol-water (containing 0.2% formic acid; 55:45, v/v). The detection was performed on a triple quadrupole tandem mass spectrometer in multiple reaction monitoring mode via an electrospray ionization source. Each plasma sample was chromatographed within 2.5 min. The linear calibration curves for lisinopril were obtained in the concentration range of 1.03-206 ng/mL (r(2)  ≥ 0.99) with a lower limit of quantification of 1.03 ng/mL. The intra- and inter-day precisions (relative standard deviation) were not higher than 11%, and accuracy (relative error) was within ±6.8%, determined from quality control samples for lisinopril, which corresponded to the guidance of the Food and Drug Administration. The method described herein was fully validated and successfully applied to the pharmacokinetic study of lisinopril tablets in healthy male volunteers after oral administration.
    Biomedical Chromatography 06/2012; 26(6):691-6. DOI:10.1002/bmc.1715 · 1.66 Impact Factor