In:
Basic & Clinical Pharmacology & Toxicology, Wiley, Vol. 132, No. 1 ( 2023-01), p. 33-50
Abstract:
A sensitive and rapid ultra‐high‐performance liquid chromatography–tandem mass spectrometry (UHPLC–MS/MS) method was successfully applied to the determination of 10 alkaloids in beagle dog plasma following a single oral dose of Xiatianwu capsules and enteric‐coated capsules, with theophylline serving as the internal standard (IS). Methods Plasma samples were preprocessed using liquid–liquid extraction (LLE) with ethyl acetate ahead to separation using a gradient elution procedure on a Waters ACQUITY UPLC HSS T3 column (1.8 μm, 100 × 2.1 mm). The mobile phase was composed of 0.1% formic acid solution and acetonitrile at the flow rate of 0.3 ml/min. Multiple reaction monitoring (MRM) was used to determine the analytes in the positive ion mode. Results The calibration curves for 10 analytes demonstrated a high degree of linearity ( r ≥ 0.9920). The lower limit of quantification (LLOQ) values for 10 alkaloids were all more than 1.074 ng/ml, and matrix effects varied from 94.25% to 106.15%. The mean extraction recovery of quality control samples at low (LQC), medium (MQC) and high (HQC) concentrations, as well as IS, was all more than 76.60%. The intra‐day and inter‐day precision ( RSD ) also satisfied the requirement. Simultaneously, the variation of assay accuracies ( RE ) was between 13.05% and 9.38%. Conclusion The test was validated in accordance with regulatory bioanalytical guidelines and was found to be suitable for use in a pharmacokinetic investigation of these compounds in beagle dogs after oral administration of Xiatianwu general capsules and enteric‐coated capsules. The C max of 10 alkaloids ranged from 52.61 to 192.46 ng/ml after oral administration of Xiatianwu capsules, and from 67.50 to 247.36 ng/ml. The T max was between 0.59 and 1.33 h of Xiatianwu capsules, and between 1.08 and 2.00 h of enteric‐coated capsules. The t 1/2 ranged from 3.18 to 7.47 h of general capsules, and from 6.01 to 11.36 h. AUC 0‐t ranged from 181.06 to 722.74 ng·h/ml of Xiatianwu capsules, and from 275.03 to 884.17 ng·h/ml of enteric‐coated capsules. The C max of enteric‐coated capsules were significantly increased except for tetrahydropalmatine and berberine. T max of general capsules were less than 1 h, and of enteric‐coated capsules were less than 2 h. The t 1/2 of dehydrocorydaline, palmatine, tetrahydrojatrorrhizine, jatrorrhizine and coptisine in enteric‐coated capsules was longer than that in ordinary capsule. The AUC 0‐t and AUC 0‐∞ of bicuculline, dehydrocorydaline, protopine, magnoflorine, tetrahydrojatrorrhizine, jatrorrhizine, berberine and coptisine were all significantly higher in enteric‐coated capsules.
Type of Medium:
Online Resource
ISSN:
1742-7835
,
1742-7843
Language:
English
Publisher:
Wiley
Publication Date:
2023
detail.hit.zdb_id:
2151592-X
SSG:
15,3
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