Abstract
Delsoline, a major alkaloid of Delphinium anthriscifolium Hance, has both a curare-like effect and a ganglion-blocking effect and is used to relieve muscle tension or hyperkinesia. A ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was established for the determination of delsoline in mouse blood, and the pharmacokinetics of delsoline after intravenous administration (1 mg/kg) and intragastric administration (9, 6, and 3 mg/kg) were studied. Gelsenicine served as an internal standard, and a UPLC BEH C18 chromatographic column was used. The mobile phase consisted of acetonitrile and 0.1% formic acid; the gradient elution flow rate was 0.4 mL/min. The MRM model was used for the quantitative analysis of delsoline m/z 468.3⟶108.1 and the internal standard m/z 327.1⟶296.1. Mouse blood samples were treated with acetonitrile precipitation to remove proteins. In the concentration range of 0.1–1000 ng/mL, delsoline in mouse blood showed a good linearity (r2 > 0.995), and the lower limit of quantitation was 0.1 ng/mL. The intraday precision relative standard deviation (RSD) was below 14%, and the interday precision RSD was below 15%. The accuracy ranged between 94.3% and 110.1%, the average recovery was above 90.8%, and the matrix effect ranged between 97.0% and 102.5%. The UPLC-MS/MS method was sensitive, rapid, and selective in the study of pharmacokinetics of delsoline. The absolute bioavailability of delsoline was 20.9%.
Highlights
Delphinium anthriscifolium Hance, belonging to the genus Delphinium of family Ranunculaceae, is a perennial herb growing in the regions of Guangdong, Guangxi, Guizhou, Hunan, and Jiangxi of China [1, 2]
E intraday precision relative standard deviation (RSD) was below 14%, and the interday precision RSD was below 15% (Table 1). e accuracy ranged between 94.3% and 110.1%, the average recovery rate was above 90.8%, and the matrix effect ranged between 97.0% and 102.5%. e above results met the requirements of the pharmacokinetic study of delsoline [12]
Pharmacokinetics Study. e pharmacokinetics of delsoline after intravenous and intragastric administration was studied using the UPLC-MS/MS method. e drug concentration-time curves are shown in Figure 3. e main pharmacokinetic parameters fitted by the noncompartment model are shown in Table 2. e t1/2 of the intragastric administration (9, 6, and 3 mg/kg) and intravenous administration (1 mg/kg) was 1.3 + 0.5 h, 1.6 + 0.7 h, 1.7 + 0.8 h, and 2.5 + 0.7 h, respectively, indicating that its metabolism was rapid. e absolute bioavailability of delsoline (9, 6, and 3 mg/kg) was 26.2%, 18.8%, and 17.7%, respectively, with an average of 20.9%. e absolute bioavailability of these doses was not significantly different
Summary
Delphinium anthriscifolium Hance, belonging to the genus Delphinium of family Ranunculaceae, is a perennial herb growing in the regions of Guangdong, Guangxi, Guizhou, Hunan, and Jiangxi of China [1, 2]. It has effects of dispelling wind and dampness, activating collaterals, and relieving pains and is used to treat rheumatism, hemiplegia, indigestion, and cough. Compared with LC-MS/MS and micellar liquid chromatography, the UPLC-MS/MS method is more sensitive and better suited for the research of pharmacokinetics [6,7,8,9,10,11]. Journal of Analytical Methods in Chemistry intravenous administration (1 mg/kg) and intragastric administration (9, 6, and 3 mg/kg), and absolute bioavailability of delsoline was obtained
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