A practical strategy for characterization of the metabolic profile of chiral drugs using combinatory liquid chromatography–mass spectrometric techniques: Application to tetrahydropalmatine enantiomers and their metabolites in rat urine

Zhang, Yinying; Dong, Xin; Jian, Le; Wen, Jing; Lin, Zebin; Liu, Yinli; Lou, Ziyang; Chai, Yifeng; Hong, Zhanying

doi:10.1016/j.jpba.2014.01.045

Cited by 20 publications

(11 citation statements)

References 22 publications

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“…Recently, there was reporting on the metabolism studies of l ‐tetrahydropalmatine in rats, 30 urinary metabolites were identified after administration of l ‐tetrahydropalmatine using UPLC‐ QTOF/MS . By comparing the metabolites of l ‐tetrahydropalmatine and l ‐isocorypalmine, we found some of them were same, but M1, M6, M7, M9 and M12 were identified only in l ‐isocorypalmine.…”

Section: Resultsmentioning

confidence: 82%

Metabolite profiling of l‐isocorypalmine in rat urine, plasma, and feces after oral administration using high performance liquid chromatography coupled to Fourier transform ion cyclotron resonance mass spectrometry

Zhang

Huai

et al. 2018

J of Separation Science

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l‐Isocorypalmine, an active alkaloid compound isolated from Rhizoma Corydalis yanhusuo, has been reported to possess biological activity for treating cocaine use disorder. A high‐performance liquid chromatography coupled to Fourier transform ion cyclotron resonance mass spectrometry method was established for identification of the metabolites of l‐isocorypalmine in urine, plasma and feces samples of rats after a single intragastric gavage of l‐isocorypalmine at a dose of 15 mg/kg. As a result, a total of 21 metabolites (six phase І metabolites and fifteen phase II metabolites) were detected and tentatively identified by mass spectrometry and fragment ions from tandem mass spectrometry spectra. All metabolites were present in the urine samples, nine metabolites were found in the plasma samples and three metabolites were found in the feces samples. Results indicated that metabolic pathways of l‐isocorypalmine included oxidation, dehydrogenation, demethylation, sulfate conjugation, and glucuronide conjugation. In addition, glucuronidation was the major metabolic reaction. Results of this investigation could provide significant experimental basis for efficacy, safety and action mechanism of l‐isocorypalmine, which will be advantageous to new drug development for treating cocaine addiction.

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Section: Resultsmentioning

confidence: 82%

Metabolite profiling of l‐isocorypalmine in rat urine, plasma, and feces after oral administration using high performance liquid chromatography coupled to Fourier transform ion cyclotron resonance mass spectrometry

Zhang

Huai

et al. 2018

J of Separation Science

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“…1). Further study [10,11] proved that L-ICP was also one of the active metabolites of L-tetrahydropalmatine (L-THP) with a mono demethylation at C-2 position (Fig. 1).…”

Section: Introductionmentioning

confidence: 95%

Pharmacokinetics, tissue distribution, and excretion studies ofl-isocorypalmine using ultra high performance liquid chromatography with tandem mass spectrometry

et al. 2017

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l-Isocorypalmine is a newly identified metabolite of l-tetrahydropalmatine with a unique dual pharmacological profile as a partial dopamine receptor 1 agonist and dopamine receptor 2 antagonist properties for treating cocaine use disorder. The purpose of this study was to explore the pharmacokinetic profiles, tissue distribution, and excretion of l-isocorypalmine in Sprague-Dawley rats. A sensitive and reliable ultra high performance liquid chromatography with tandem mass spectrometry method was developed and validated for determination of l-isocorypalmine in biological samples. The biological samples were extracted by liquid-liquid extraction and separated on a Bonshell ASB C column (2.1 × 100 mm, 2.7 μm, Agela) with gradient mobile phase at the flow rate of 0.2 mL/min. The detection was performed by positive electrospray ionization with multiple reaction monitoring mode. Satisfactory linearity, precision, accuracy, extraction recovery, and acceptable matrix effect were achieved. The quantitative method was successfully applied to the pharmacokinetics, tissue distribution, and excretion study of l-isocorypalmine. The results showed that l-isocorypalmine was rapidly distributed, and eliminated from rat plasma and manifested linear dynamics in a dose range of 7.5-15 mg/kg. In addition, the results would be helpful for further clinical reference of l-isocorypalmine as a potential candidate drug for the treatment of cocaine addiction.

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“…Metabolism studies of L-THP in rats revealed that 30 urinary metabolites were identified after administration of L-THP using UPLC-QTOF/MS, and the major metabolites are L-isocorypalmine (L-ICP), L-corypalmine (L-CP), L-corydalmine (L-CD) and L-tetrahydropalmatrubine, with mono demethylation at C-2, C-3, C-9 and C-10 position, respectively (Zhang et al , 2014). Among them (Ma et al, 2008; Wang et al, 2012; Sasaki et al, 2010), L-ICP was recently characterized to reduce behavioral sensitization and rewarding effects of cocaine in mice.…”

Section: Introductionmentioning

confidence: 99%

Simultaneous determination of l‐tetrahydropalmatine and its active metabolites in rat plasma by a sensitive ultra‐high‐performance liquid chromatography with tandem mass spectrometry method and its application in a pharmacokinetic study

Wang

Liu

Zhao

et al. 2017

Biomedical Chromatography

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A sensitive and reliable ultra high performance liquid chromatography with tandem mass spectrometry (UHPLC-MS/MS) method was developed and validated for simultaneous determination of L-tetrahydropalmatine (L-THP) and its active metabolites L-isocorypalmine (L-ICP) and L-corydalmine (L-CD) in rat plasma,. The analytes were extracted by liquid-liquid extraction and separated on a Bonshell ASB C18 column (2.1 mm×100 mm; 2.7 μm; Agela) using acetonitrile-formic acid aqueous as mobile phase at a flow rate of 0.2 mL/min in gradient mode. The method was validated over the concentration range of 4.00–2,500 ng/mL for L-THP, 0.400–250 ng/mL for L-ICP and 1.00–625 ng/mL for L-CD, respectively. Intra- and inter-day accuracy and precision were within the acceptable limits of less than 15% at all concentrations. Correlation coefficients (r) for the calibration curves were more than 0.99 for all analytes. The quantitative method was successfully applied for simultaneous determination of L-THP and its active metabolites in a pharmacokinetic study after oral administration with L-THP at the dose of 15 mg/kg to rats.

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A practical strategy for characterization of the metabolic profile of chiral drugs using combinatory liquid chromatography–mass spectrometric techniques: Application to tetrahydropalmatine enantiomers and their metabolites in rat urine

Cited by 20 publications

References 22 publications

Metabolite profiling of l‐isocorypalmine in rat urine, plasma, and feces after oral administration using high performance liquid chromatography coupled to Fourier transform ion cyclotron resonance mass spectrometry

Metabolite profiling of l‐isocorypalmine in rat urine, plasma, and feces after oral administration using high performance liquid chromatography coupled to Fourier transform ion cyclotron resonance mass spectrometry

Pharmacokinetics, tissue distribution, and excretion studies ofl-isocorypalmine using ultra high performance liquid chromatography with tandem mass spectrometry

Simultaneous determination of l‐tetrahydropalmatine and its active metabolites in rat plasma by a sensitive ultra‐high‐performance liquid chromatography with tandem mass spectrometry method and its application in a pharmacokinetic study

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