Abstract

A rapid and sensitive Ultra high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed for the simultaneous determination of fourteen alkaloids in beagle dog plasma after a single oral dose of the Corydalis bungeana Turcz (C. bungeana) extract selected bifendate as the internal standard (IS). The plasma samples were preprocessed by liquid-liquid extraction (LLE) with aether before separation on an Agilent SB-C18 column (1.8 µm, 150 × 2.1 mm) using a gradient elution program. The mobile phase consists of 0.2% acetic acid and acetonitrile at the flow rate of 0.3 mL/min. In the positive ion mode, the analytes were detected by multiple reaction monitoring (MRM). The results indicated that calibration curves for fourteen analytes have good linearity (R2 = 0.9904). The lower limits of quantification (LLOQ) of fourteen alkaloids and IS were all over 4.87 ng/mL and the matrix effects ranged from 94.08% to 102.76%. The mean extraction recoveries of Quality control samples at low (LQC), medium (MQC) and high (HQC) and IS were all more than 78.03%. The intra- and inter-day precision (R.S.D.%) also met the criterion, at the same time the deviation of assay accuracies (R.E) ranged from −13.70% to 14.40%. The Tmax values of fourteen alkaloids were no more than 1 h. The range of Cmax was from 74.16 ± 8.71 to 2256 ± 255.9 ng/mL. The assay was validated in the light of the regulatory bioanalytical guidelines and proved acceptable, which was successfully applied to a pharmacokinetic study of these compounds in beagle dogs after oral administration of Corydalis bungeana Turcz extract.

Highlights

  • Corydalis bungeana Turcz. (C. bungeana), known as “Diding”, “Kuding” or “Xiaojicai” and first seen in the “Annals of traditional Chinese Medicine,” belongs to the Papaveraceae family

  • Due to the complexity of the detection method, the MS/MS ion transitions were taken in multiple reaction monitoring (MRM)

  • The fragmentors were at 180 V for acetylcorynoline, 170 V for protopine and 8-oxocorynoline, 140 V for Z23, 147 V for coptisine, 160 V

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Summary

Introduction

Corydalis bungeana Turcz. (C. bungeana), known as “Diding”, “Kuding” or “Xiaojicai” and first seen in the “Annals of traditional Chinese Medicine,” belongs to the Papaveraceae family. (C. bungeana), known as “Diding”, “Kuding” or “Xiaojicai” and first seen in the “Annals of traditional Chinese Medicine,” belongs to the Papaveraceae family. Molecules 2018, 23, 1927 whole plant is referred in traditional Chinese medicine (TCM) as Herba Corydalis Bungeanae and is officially listed in Chinese Pharmacopoeia [1]. It is a perennial herb with violet to pink flowers distributed in the northern and eastern parts of China, the southeast of Mongolia, the northern part of the Korean peninsula and the far east of Russia. C. bungeana has such a good anti-inflammatory effect due to restrain the activation of NF-κB signaling pathway through inhibiting phosphorylation of IκBα and p65. C. bungeana clinically was applied in many traditional formulas, such as Ganmaoqingre Granules and Cholagogic

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