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Quantification of Lappaconitine in Mouse Blood by UPLC-MS/MS and Its Application to a Pharmacokinetic Study.
Biomed Res Int 2019; 2019:6262105BR

Abstract

Lappaconitine is extracted from Aconitum sinomontanum Nakai, which belongs to the Ranunculaceae. Lappaconitine is as a diterpenoid alkaloid used as a nonaddictive analgesic. To assure the rational use of the drug, ultrahigh-pressure liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was conducted to determine lappaconitine in mouse blood and its application to pharmacokinetics. In this study, khasianine was used as internet standard (IS). A UPLC BEH C18 column was used for chromatographic separation and the mobile phase consisted of acetonitrile and 10 mmol/L ammonium acetate (0.1% formic acid). The flow rate of was 0.4 mL/min. Quantitative detection was performed in a multiple reaction monitoring (MRM) mode using an electrospray ionization source in positive mode. Twenty-four mice were randomly divided into four groups, three of which received 2, 4, and 8 mg/kg lappaconitine by intragastric administration, while the other group received 1 mg/kg lappaconitine by intravenous administration. After 0.0833, 0.5, 1, 1.5, 2, 3, 4, and 8 h, blood samples were collected and acetonitrile was used for protein precipitation. A linear calibration relationship (R2 = 0.9979) in the range of 0.1-500 ng/mL in mouse blood indicated good results. The lower limit of quantitation was 0.1 ng/mL and the limit of detection was 0.04 ng/mL. The intra-day and inter-day precision were below 13% and 14%, respectively. The accuracy was 90.1-107.2%, and the recovery exceeded 81.1%. The matrix effect ranged between 102.1 and 108.8%. The absolute bioavailability of lappaconitine was 2.0%. UPLC-MS/MS achieved high sensitivity, speed, and selectivity. Methodological verification indicated this method as suitable for determination of lappaconitine in mouse blood.

Authors+Show Affiliations

Ruian People's Hospital, The Third Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.Ruian People's Hospital, The Third Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.Ruian People's Hospital, The Third Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.Laboratory Animal Centre, Wenzhou Medical University, Wenzhou 325035, China.Laboratory Animal Centre, Wenzhou Medical University, Wenzhou 325035, China.Laboratory Animal Centre, Wenzhou Medical University, Wenzhou 325035, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30723741

Citation

Chen, Fan, et al. "Quantification of Lappaconitine in Mouse Blood By UPLC-MS/MS and Its Application to a Pharmacokinetic Study." BioMed Research International, vol. 2019, 2019, p. 6262105.
Chen F, Shen X, Huang P, et al. Quantification of Lappaconitine in Mouse Blood by UPLC-MS/MS and Its Application to a Pharmacokinetic Study. Biomed Res Int. 2019;2019:6262105.
Chen, F., Shen, X., Huang, P., Fu, H., Jin, Y., & Wen, C. (2019). Quantification of Lappaconitine in Mouse Blood by UPLC-MS/MS and Its Application to a Pharmacokinetic Study. BioMed Research International, 2019, p. 6262105. doi:10.1155/2019/6262105.
Chen F, et al. Quantification of Lappaconitine in Mouse Blood By UPLC-MS/MS and Its Application to a Pharmacokinetic Study. Biomed Res Int. 2019;2019:6262105. PubMed PMID: 30723741.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Quantification of Lappaconitine in Mouse Blood by UPLC-MS/MS and Its Application to a Pharmacokinetic Study. AU - Chen,Fan, AU - Shen,Xiuwei, AU - Huang,Peng, AU - Fu,Huiyan, AU - Jin,Yue, AU - Wen,Congcong, Y1 - 2019/01/06/ PY - 2018/07/17/received PY - 2018/10/19/revised PY - 2018/12/26/accepted PY - 2019/2/7/entrez PY - 2019/2/7/pubmed PY - 2019/5/31/medline SP - 6262105 EP - 6262105 JF - BioMed research international JO - Biomed Res Int VL - 2019 N2 - Lappaconitine is extracted from Aconitum sinomontanum Nakai, which belongs to the Ranunculaceae. Lappaconitine is as a diterpenoid alkaloid used as a nonaddictive analgesic. To assure the rational use of the drug, ultrahigh-pressure liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was conducted to determine lappaconitine in mouse blood and its application to pharmacokinetics. In this study, khasianine was used as internet standard (IS). A UPLC BEH C18 column was used for chromatographic separation and the mobile phase consisted of acetonitrile and 10 mmol/L ammonium acetate (0.1% formic acid). The flow rate of was 0.4 mL/min. Quantitative detection was performed in a multiple reaction monitoring (MRM) mode using an electrospray ionization source in positive mode. Twenty-four mice were randomly divided into four groups, three of which received 2, 4, and 8 mg/kg lappaconitine by intragastric administration, while the other group received 1 mg/kg lappaconitine by intravenous administration. After 0.0833, 0.5, 1, 1.5, 2, 3, 4, and 8 h, blood samples were collected and acetonitrile was used for protein precipitation. A linear calibration relationship (R2 = 0.9979) in the range of 0.1-500 ng/mL in mouse blood indicated good results. The lower limit of quantitation was 0.1 ng/mL and the limit of detection was 0.04 ng/mL. The intra-day and inter-day precision were below 13% and 14%, respectively. The accuracy was 90.1-107.2%, and the recovery exceeded 81.1%. The matrix effect ranged between 102.1 and 108.8%. The absolute bioavailability of lappaconitine was 2.0%. UPLC-MS/MS achieved high sensitivity, speed, and selectivity. Methodological verification indicated this method as suitable for determination of lappaconitine in mouse blood. SN - 2314-6141 UR - https://www.unboundmedicine.com/medline/citation/30723741/Quantification_of_Lappaconitine_in_Mouse_Blood_by_UPLC_MS/MS_and_Its_Application_to_a_Pharmacokinetic_Study_ L2 - https://dx.doi.org/10.1155/2019/6262105 DB - PRIME DP - Unbound Medicine ER -