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UPLC-MS/MS determination and gender-related pharmacokinetic study of five active ingredients in rat plasma after oral administration of Eucommia cortex extract.
J Ethnopharmacol. 2015 Jul 01; 169:145-55.JE

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Eucommiae cortex (EC), the bark of Eucommia ulmoides Oliv., has been traditionally used to treat many diseases in China for more than 2000 years. The pharmacological effects are primarily attributed to the presence of lignans, iridoids and phenolics, which are main active ingredients in EC.

AIM OF THE STUDY

First, to investigate the active ingredients that can be absorbed into the rat plasma according to which ingredients exhibit significant correlation of drug concentration-time curve. Second, to establish an efficient ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) method for simultaneous determination of ingredients absorbed in rat plasma. Finally, to investigate gender effect on the pharmacokinetics of the ingredients absorbed in male and female rats plasma after oral administration with EC extract.

MATERIALS AND METHODS

18 ingredients from EC were detected by UPLC-MS/MS, 9 out of 18 ingredients were absorbed into rat plasma. And 5 ingredients exhibit significant correlation of drug concentration-time curve. They were pinoresinol di-O-β-d-glucopyranoside (PDG), geniposide (GE), geniposidic acid (GA), aucubin (AN) and chlorogenic acid (CA). The analytes were extracted from rat plasma via a simple protein precipitation procedure and osalmid was used as the internal standard. Chromatographic separation was achieved on a Waters ACQUITY HSS T3 column (2.1mm×100mm, 1.8μm) using a gradient elution program with acetonitrile and 0.1% formic acid water as the mobile phase, with a flow rate of 0.3mLmin(-1). The detection was performed on a triple-quadrupole tandem mass spectrometer by multiple reactions monitoring (MRM) mode in a positive ion mode via electrospray ionization (ESI). The transition monitored were /z 683.00[M+H](+)→235.10 for PDG, / z 389.00[M+H](+)→208.80 for GE, m/z 375.00[M+H](+)→194.79 for GA, m/z 364.00[M+NH4](+)→148.81 for AN, m/z 355.10[M+H](+)→162.84 for CA and m/z 230.03[M+H](+)→120.77 for internal standard.

RESULTS

The developed method showed good linearity over a wide concentration range, the lower limits of quantification and higher accuracy and precision for determination of the 5 analytes. Then the method was applied to study the pharmacokinetics in rats, and the results indicated that there were significant differences in pharmacokinetic parameters of the analytes between the male and female rats, and absorptions of these analytes in male group were all significantly higher than those in female group.

CONCLUSION

This study established an efficient, sensitive and selective UPLC-MS/MS method for simultaneous determination of the five ingredients in rat plasma, and it could be successfully applied to the comparative pharmacokinetic studies in male and female rats after oral administration with EC extract.

Authors+Show Affiliations

School of Pharmacy, Lanzhou University, Lanzhou 730000, China; The MOE Key Laboratory for Standardization of Chinese Medicines and The Key Laboratory for Pharmacology of Compound Chinese Medicine of Shanghai, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.School of Pharmacy, Lanzhou University, Lanzhou 730000, China; Hong-Hui Hospital, Xi׳an Jiaotong University College of Medicine, Xi׳an, China.School of Pharmacy, Lanzhou University, Lanzhou 730000, China.The MOE Key Laboratory for Standardization of Chinese Medicines and The Key Laboratory for Pharmacology of Compound Chinese Medicine of Shanghai, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Research Center for Traditional Chinese Medicine of Complexity System, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.School of Pharmacy, Lanzhou University, Lanzhou 730000, China.The MOE Key Laboratory for Standardization of Chinese Medicines and The Key Laboratory for Pharmacology of Compound Chinese Medicine of Shanghai, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Research Center for Traditional Chinese Medicine of Complexity System, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.The MOE Key Laboratory for Standardization of Chinese Medicines and The Key Laboratory for Pharmacology of Compound Chinese Medicine of Shanghai, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Research Center for Traditional Chinese Medicine of Complexity System, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address: wangzht@shutcm.edu.cn.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25910535

Citation

Hu, Fangdi, et al. "UPLC-MS/MS Determination and Gender-related Pharmacokinetic Study of Five Active Ingredients in Rat Plasma After Oral Administration of Eucommia Cortex Extract." Journal of Ethnopharmacology, vol. 169, 2015, pp. 145-55.
Hu F, An J, Li W, et al. UPLC-MS/MS determination and gender-related pharmacokinetic study of five active ingredients in rat plasma after oral administration of Eucommia cortex extract. J Ethnopharmacol. 2015;169:145-55.
Hu, F., An, J., Li, W., Zhang, Z., Chen, W., Wang, C., & Wang, Z. (2015). UPLC-MS/MS determination and gender-related pharmacokinetic study of five active ingredients in rat plasma after oral administration of Eucommia cortex extract. Journal of Ethnopharmacology, 169, 145-55. https://doi.org/10.1016/j.jep.2015.04.007
Hu F, et al. UPLC-MS/MS Determination and Gender-related Pharmacokinetic Study of Five Active Ingredients in Rat Plasma After Oral Administration of Eucommia Cortex Extract. J Ethnopharmacol. 2015 Jul 1;169:145-55. PubMed PMID: 25910535.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - UPLC-MS/MS determination and gender-related pharmacokinetic study of five active ingredients in rat plasma after oral administration of Eucommia cortex extract. AU - Hu,Fangdi, AU - An,Jing, AU - Li,Wen, AU - Zhang,Zijia, AU - Chen,Wenxia, AU - Wang,Changhong, AU - Wang,Zhengtao, Y1 - 2015/04/22/ PY - 2014/09/26/received PY - 2015/04/08/revised PY - 2015/04/10/accepted PY - 2015/4/26/entrez PY - 2015/4/26/pubmed PY - 2016/3/2/medline KW - Aucubin KW - Aucubin (PubChem CID: 91458) KW - Chlorogenic acid KW - Chlorogenic acid (PubChem CID: 1794427) KW - Epipinoresinol (PubChem CID: 637584) KW - Eucommia cortex KW - Geniposide KW - Geniposide (PubChem CID: 107848) KW - Geniposidic acid KW - Geniposidic acid (PubChem CID: 443354) KW - Medioresinol (PubChem CID: 181681) KW - Pharmacokinetics KW - Pinoresinol (PubChem CID: 73399) KW - Pinoresinol di-O-β-d-glucopyranoside KW - Pinoresinol di-O-β-d-glucopyranoside (PubChem CID:44202790) KW - Rat plasma KW - Rutin (PubChem CID: 5280805) KW - Syringaresinol (PubChem CID: 443023) KW - UPLC-MS/MS SP - 145 EP - 55 JF - Journal of ethnopharmacology JO - J Ethnopharmacol VL - 169 N2 - ETHNOPHARMACOLOGICAL RELEVANCE: Eucommiae cortex (EC), the bark of Eucommia ulmoides Oliv., has been traditionally used to treat many diseases in China for more than 2000 years. The pharmacological effects are primarily attributed to the presence of lignans, iridoids and phenolics, which are main active ingredients in EC. AIM OF THE STUDY: First, to investigate the active ingredients that can be absorbed into the rat plasma according to which ingredients exhibit significant correlation of drug concentration-time curve. Second, to establish an efficient ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) method for simultaneous determination of ingredients absorbed in rat plasma. Finally, to investigate gender effect on the pharmacokinetics of the ingredients absorbed in male and female rats plasma after oral administration with EC extract. MATERIALS AND METHODS: 18 ingredients from EC were detected by UPLC-MS/MS, 9 out of 18 ingredients were absorbed into rat plasma. And 5 ingredients exhibit significant correlation of drug concentration-time curve. They were pinoresinol di-O-β-d-glucopyranoside (PDG), geniposide (GE), geniposidic acid (GA), aucubin (AN) and chlorogenic acid (CA). The analytes were extracted from rat plasma via a simple protein precipitation procedure and osalmid was used as the internal standard. Chromatographic separation was achieved on a Waters ACQUITY HSS T3 column (2.1mm×100mm, 1.8μm) using a gradient elution program with acetonitrile and 0.1% formic acid water as the mobile phase, with a flow rate of 0.3mLmin(-1). The detection was performed on a triple-quadrupole tandem mass spectrometer by multiple reactions monitoring (MRM) mode in a positive ion mode via electrospray ionization (ESI). The transition monitored were /z 683.00[M+H](+)→235.10 for PDG, / z 389.00[M+H](+)→208.80 for GE, m/z 375.00[M+H](+)→194.79 for GA, m/z 364.00[M+NH4](+)→148.81 for AN, m/z 355.10[M+H](+)→162.84 for CA and m/z 230.03[M+H](+)→120.77 for internal standard. RESULTS: The developed method showed good linearity over a wide concentration range, the lower limits of quantification and higher accuracy and precision for determination of the 5 analytes. Then the method was applied to study the pharmacokinetics in rats, and the results indicated that there were significant differences in pharmacokinetic parameters of the analytes between the male and female rats, and absorptions of these analytes in male group were all significantly higher than those in female group. CONCLUSION: This study established an efficient, sensitive and selective UPLC-MS/MS method for simultaneous determination of the five ingredients in rat plasma, and it could be successfully applied to the comparative pharmacokinetic studies in male and female rats after oral administration with EC extract. SN - 1872-7573 UR - https://www.unboundmedicine.com/medline/citation/25910535/UPLC_MS/MS_determination_and_gender_related_pharmacokinetic_study_of_five_active_ingredients_in_rat_plasma_after_oral_administration_of_Eucommia_cortex_extract_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-8741(15)00258-5 DB - PRIME DP - Unbound Medicine ER -