Comparative study on effects of single and multiple oral administration of mungbean (Phaseolus radiatus L.) seed extract on the pharmacokinetics of aconitine by UHPLC-MS Enze Gao, Xiaohan Yu † , Ting Liu † , Hualing Li, Pei Wang, Yingqing Wei, Yunli Zhao and Zhiguo Yu* ABSTRACT: The study was aimed to investigate the effects of single and multiple oral administration of mungbean (Phaseolus radiatus L.) seed extract (ME) on the pharmacokinetics of aconitine in rats. The Sprague–Dawley rats were randomly divided into three groups (six rats each group). In group 1, rats were orally administered 500 μg/kg aconitine after receiving a single oral dose of 1 g/kg ME. In group 2, rats were orally administered with 500 μg/kg aconitine at day 7 of treatment with 1 g/kg/day ME. In group 3, rats were orally administered with 500 μg/kg aconitine. Blood samples were collected at different time points (0.083, 0.25, 0.5, 1.0, 1.5, 2.0, 4.0, 6.0, 8.0 and 10.0h). The concentration of aconitine in rats plasma was determined by a fully validated ultra-high-performance liquid chromatography coupled with mass spectrometry method. The results showed that single and multiple oral co-administration of ME significantly altered the pharmacokinetic parameters of aconitine. Copyright © 2014 John Wiley & Sons, Ltd. Keywords: aconitine; quantitative analysis; pharmacokinetics; Phaseolus radiatus L; UHPLC-MS Introduction The genus Aconitum consists of more than 200 species in China. The best-known species is Aconitum napellus (Monk’s hood wolfsbane, aconite). Among them, only two species (Aconitum carmichaeli Debx and Aconitum kusnezoffi Reichb) are used in Chinese materia medica (Singhuber et al., 2009; Wang et al., 2009). Aconitum alkaloids are the main bioactive components in Aconitum carmichaeli Debx (a famous Chinese medicinal herb for the treatment of colds, polyarthralgia, diarrhea, heart failure, beriberi and edema for thousands of years; Murayama et al., 1991). They contributed to its pharmacological efficacy as well as toxicity (Peng et al., 2013). Among those alkaloids, aconitine is the foremost highly toxic diester-diterpene in Aconitum carmichaeli Debx (Chen et al., 2008; Hikino et al., 1983). This alkaloid has a narrow therapeutic index. Owing to the toxicity of Aconitum alkaloids, raw radix of Aconitum carmichaeli Debx is used only after processing. However, poisoning may still occur even after the consumption of processed radix of Aconitum carmichaeli Debx (Tai et al., 1992). Thus, in order to reduce the toxicity and increase the efficacy, radix of Aconitum carmichaeli Debx is used in combination with other herbs or components, such as Radix Glycyrrhizae (Shen et al., 2011), Rhizome Atractylodes (Xin et al., 2011), Radix Paeonia (Fan et al., 2012) and diammonium glycyrrhizinate (Chen et al., 2009). Furthermore, more researchers have begun to focus on the compound interactions in the herb-pairs. The first stage requires an in-depth understanding of its pharmacokinetic properties. Mungbean (Phaseolus radiates L.) seed has traditionally been used as a health food in Asia. It is a good source of essential fatty acids, minerals and tocopherols (Anwar et al., 2007). Now, much attention has been devoted to it for its physiological functional- ities, owing to its bioactive phytochemicals, such as vitexin, isovitexin and D-chiro-inositol (DOI; Li et al., 2011; Yao et al., 2008, 2011). The application of mungbean as a treatment for acute toxicity of Fuzi (Aconitum carmichaeli Debx) was first recorded in Ben-Cao-Gang-Mu (Compendium of Materia Medica). However, the mechanism underlying its detoxifying effect on the acute toxicity of Aconitum carmichaeli Debx is unknown. Therefore, the main purpose of the present study is to explore those mechanisms by comparing the pharmacoki- netic parameters of aconitine as a targeted marker of Aconitum carmichaeli Debx between administration of aconitine alone and single or multiple co-administration of mungbean (Phaseolus radiatus L.) seed extract (ME). Recently, research on the pharmacokinetics of Aconitum alkaloids after oral administration of radix of Aconitum carmichaeli Debx alone or co-administration of other herbs as herb-pairs has been carried out (Fan et al., 2012; Shen et al., * Correspondence to: Z. Yu, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China. Email: zhiguo-yu@163.com † These authors contributed equally to this work and should be regarded as co-second authors. School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China Abbreviations used: DOI, D-chiro-inositol; ESI, electrospray ionization; ME, mungbean (Phaseolus radiatus L.) seed extract. Biomed. Chromatogr. 2014; 28: 1313–1319 Copyright © 2014 John Wiley & Sons, Ltd. Research article Received: 12 November 2013, Revised: 19 December 2013, Accepted: 17 January 2014 Published online in Wiley Online Library: 3 March 2014 (wileyonlinelibrary.com) DOI 10.1002/bmc.3163 1313