HPLC-MS/MS Analysis of Aconiti Lateralis Radix Praeparata and Its Combination with Red Ginseng Effect on Rat CYP450 Activities Using the Cocktail Approach.

Wenjuan Ma,Wei Wang,Guangzhe Yao,Yanxu Chang,Jun He,Huizi Ouyang,Jiayuan Shen,Qi Jia,Xuhua Huang

doi:10.1155/2020/8603934

Abstract

Red ginseng is often combined with Aconiti Lateralis Radix Praeparata to reduce alkaloids-related toxicity of the latter. Such herb-pairing also results in better therapeutic effect in heart failure, as compared to the singular use of either herb. The purpose of this study was to investigate the effect of Aconiti Lateralis Radix Praeparata and its combination with red ginseng on the activities of CYP450 enzymes in rats. A sensitive and reliable HPLC-MS/MS method was established and validated for the simultaneous determination of eight probe drugs, phenacetin (CYP1A2), tolbutamide (CYP2C9), omeprazole (CYP2C19), dextromethorphan (CYP2D6), dapsone (CYP3A4), 7-hydroxycoumarin (CYP2A6), bupropion (CYP2B6), and amodiaquine (CYP2C8), in rat plasma using diazepam as internal standard (IS). The chromatographic separation was performed on a Waters XBridge™ C18 column (2.1 mm × 100 mm, 3.5 μm) using a gradient elution with the mobile phase consisting of acetonitrile and water (containing 0.1% formic acid) at a flow rate of 0.3 mL/min. The method was successfully applied in evaluating the effect of Aconiti Lateralis Radix Praeparata and red ginseng on the activities of CYP450 enzymes. The pharmacokinetic results of the eight probe drugs suggested that Aconiti Lateralis Radix Praeparata may inhibit the activity of CYP2A6, CYP2C19, CYP2B6, CYP1A2, CYP3A4, and CYP2C9 enzymes in rats. Comparison between the two groups, Aconiti Lateralis Radix Praeparata combined with red ginseng and Aconiti Lateralis Radix Praeparata, indicated that red ginseng may inhibit the activity of CYP2D6 and CYP2B6 enzymes while inducing the activity of CYP1A2, CYP3A4, and CYP2C9 enzymes.

Highlights

Aconiti Lateralis Radix Praeparata (“Fuzi” in Chinese), recorded in Chinese Pharmacopoeia (2015 edition), is the lateral root of Aconitum carmichaelii Debx., belonging to family Ranunculaceae
Previous studies have found that the combination of red ginseng and Aconiti Lateralis Radix Praeparata is able to reduce the contents of diester diterpenoid alkaloids and increase the contents of monoester diterpenoid alkaloids in Aconiti Lateralis Radix Praeparata, strengthening the therapeutic effect of Aconiti Lateralis Radix Praeparata while decreasing its toxicity [6, 7]
The specificity of the method was investigated by comparing chromatograms of blank plasma samples from six different rats, blank plasma spiked with the eight probe drugs and IS, and a rat plasma sample after the tail vein administration of cocktail probes

Summary

Introduction

Aconiti Lateralis Radix Praeparata (“Fuzi” in Chinese), recorded in Chinese Pharmacopoeia (2015 edition), is the lateral root of Aconitum carmichaelii Debx., belonging to family Ranunculaceae. The major chemical components of Aconiti Lateralis Radix Praeparata are alkaloids including diester diterpenoid alkaloids, monoester diterpenoid alkaloids, and lipid alkaloids. Aconiti Lateralis Radix Praeparata is commonly prescribed with red ginseng Previous studies have found that the combination of red ginseng and Aconiti Lateralis Radix Praeparata is able to reduce the contents of diester diterpenoid alkaloids (hypaconitine and deoxyaconitine) and increase the contents of monoester diterpenoid alkaloids (benzoylmesaconine and benzoylhypaconine) in Aconiti Lateralis Radix Praeparata, strengthening the therapeutic effect of Aconiti Lateralis Radix Praeparata while decreasing its toxicity [6, 7]

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Conclusion