Simultaneous quantification of nine aconitum alkaloids in Aconiti Lateralis Radix Praeparata and related products using UHPLC\u2013QQQ\u2013MS/MS

Fan He,Hua Zhou,Can-Jian Wang,Ying Xie,Zhong-Qiu Liu,Chun-Song Cheng,Liang Liu

doi:10.1038/s41598-017-13499-6

Abstract

Aconiti Lateralis Radix Praeparata (Fuzi) is obtained from processed daughter roots of Aconitum carmichaeli, a toxic plant with a high medical value well known in Chinese medicine. In addition to the known toxic alkaloids (aconitine, mesaconitine, and hypaconitine) and bioactive alkaloids (benzoylaconine, benzoylmesaconine, and benzoylhypaconine), three rarely found alkaloids have been previously reported in Fuzi, i.e., yunaconitine, 8-deacetyl-yunaconitine, and crassicauline A, and they were reported in recent years to cause potential risk to patients who took Fuzi or related products. To better control the quality of this herb and its related products and ensure safe use, developing a method to simultaneously determine these 9 alkaloids is important. In this research, sensitive and accurate ultra-high-performance liquid chromatography coupled with triple quadrupole mass spectrometry method was established and used to examine 51 Fuzi and 27 Fuzi-containing products. Unexpectedly, 8-deacetyl-yunaconitine was detected in 17 Fuzi samples (33.3%) and 3 Fuzi-containing products (11.1%); yunaconitine in 10 Fuzi samples (19.6%) and 10 Fuzi-containing products (37.0%); and crassicauline A in 3 Fuzi samples (5.8%). Industry and clinics should be aware of the unusually high detection rate of these three toxic alkaloids in the Fuzi herb and its related products and take the necessary precautions to protect patients from any potential risk.

Highlights

Aconiti Lateralis Radix Praeparata (Fuzi in Pinyin), the processed daughter root of Aconitum carmichaeli Debx. (Family Ranunculaceae), is a well-known Chinese medical material recorded in the Chinese Pharmacopoeia (CHP)[1] and other traditional Chinese medicine (TCM) texts
The high-performance liquid chromatography (HPLC) and liquid chromatography hyphenated with mass spectrometry (LC/MS) methods have been broadly applied for the quantification of aconitum alkaloids in herb or herbal products and body fluids over the past few years[12,13,14,15,16,17,18], the maximum number of aconitum alkaloids simultaneously determined using these methods is only 7, i.e., AC, MA, HA, BAC, BMA, BHA, and YAC
3 active alkaloids and 6 toxic alkaloids in Fuzi were selected as chemical markers for quality control

Summary

Introduction

Aconiti Lateralis Radix Praeparata (Fuzi in Pinyin), the processed daughter root of Aconitum carmichaeli Debx. (Family Ranunculaceae), is a well-known Chinese medical material recorded in the Chinese Pharmacopoeia (CHP)[1] and other traditional Chinese medicine (TCM) texts. Crude Fuzi must be processed by heating or steaming, and processed Fuzi must be boiled before oral administration according to TCM theories and practice During these processes, aconitine (AC), mesaconitine (MA), and hypaconitine (HA), which are the main toxic DDAs in Fuzi, degrade into less toxic but still active monoester-diterpenoid alkaloids (MDAs), such as benzoylaconine (BAC), benzoylmesaconine (BMA), and benzoylhypaconine (BHA), respectively[6]. In the 17 cases reported in Hong Kong, yunaconitine (YAC), crassicauline A (CCA), and 8-deacetyl-yunaconitine (DYA) were detected instead of AC, MA and HA in the urine samples of the aconitum poisoning patients[7,9]. Because YAC, DYA and CCA were detected in the urine of the aconitum poisoning patients, these alkaloids are considered to be hidden risk factors and should be covered in laboratory screenings for toxic compounds[9]. In addition to quality control for Fuzi and its preparations, this method is valuable for toxicological and forensic studies of related samples

Methods

Results

Conclusion