# Simultaneous Determination of 12 Marker Components in Yeonkyopaedok-san Using HPLC-PDA and LC-MS/MS
## 1 Introduction  
Traditional Korean medicine (TKM), traditional Chinese medicine (TCM), and Kampo medicine (KM) generally use chemically active complexes composed of two or more medicinal herbs. They are been used for thousands of years for the prevention or treatment of various diseases. However, scientific evidence pertaining to the safety and standardization of TKM, TCM, and KM is lacking; this information is now required. Yeonkyopaedok-san (YPS), also known as Lian Qiao Bai Du San in Chinese, is a TKM. It is made up of extracts from the following 14 herbs: Forsythiae Fructus, Lonicerae Flos, Schizonepetae Spica, Saposhnikoviae Radix, Osterici seu Notopterygii Radix et Rhizoma, Araliae Continentalis Radix, Bupleuri Radix, Cnidii Rhizoma, Aurantii Fructus Immaturus, Platycodonis Radix, Poria Sclerotium, Glycyrrhizae Radix et Rhizoma, Menthae Herba, and Zingiberis Rhizoma Recens [1].  
As reported in the Dongeuibogam (representative source of the Korean medicine), YPS has been used in the initial treatment of boils. It has anti-inflammatory effects (i.e., for treatment of colds, allergies, and dermatitis) and antiatherogenic effects [1; 2; 3]. Recently, [PERSON] et al. [4; 5] reported ahigh-performance liquid chromatography (HPLC)-diode array detection and micellar electrokinetic chromatography assays for quality control of Lianqiao Baidu pills (LBP). In China, LBP is used for the treatment of diseases similar to those treated by YPS in Korea [4,5]. However, LBP is a completely different herbal formulation, consisting of 19 herbal medicines [6]. Although some studies on the efficacy of the TKM and YPS have been reported, there are no documented standardization studies which include a quality evaluation.  
The chemical composition of the main 14 raw materials constituting YPS is as follows: lignans (e.g., arcigenin (ARC) and pinoresinol) from Forsythiae Fracttus [7,8], phenylpropanoids (e.g., chlorogenic acid) from Lonicerae Flos [9], monoterpenoids (e.g., pulegone) from Schizonepetea Spica [10], flavonoids (e.g., cimifugin) and chromosomes (e.g., cimifugin 7-glucose (CFG) and 5-\(O\)-methylvisammioside (5-MVS)) from Saposhnikoviiae Radix [11], coumarins (e.g., oxypeucedanin hydrate (OPDH) and imperatorin) from Osterici seu Notopterygii Radix et Rhizoma [12], triterpenoids (e.g., kaurenoic acid and continentalic acid) from Araliae Continentalis Radix [13], triterpenoid saponins (e.g., saikosaponin A) from Bupleuri Radix [14], phenylpropanoids (e.g., ferulic acid (FA)) from Cnidia Rhiza [15], flavonoids (e.g., naringin (NAG)) and flavonoid glucosides (e.g., NAG, and neohesperidin (NHES)) from Aurantii Fractus Immaturus [16], triterpenoid saponins (e.g., platycodin D and platycodin D2) from Platycodonis Radix [17], triterpenoids (e.g., polyporenic acid C and pachymic acid) from Poria Sclerotium [18], triterpenoid saponins (e.g., glycyrrhizinic acid) and flavonoids (e.g., liquiritin apioside) from Glycyrrhiziae Radix et Rhiza [19], monoterpenoids (e.g., menthone and menthol) from Menthae Herba [20], and phenols (e.g., 6-, 8, and 10-gingerol) from Zingiberis Rhizo Recens [21].  
In this study, a simultaneous analysis of the 12 marker compounds for a quality assessment of YPS was carried out using HPLC-photodiode array detection (PDA) and an ultra-performance liquid chromatography-mass spectrometry with tandem mass spectrometry (UPLC-MS/MS). The investigated 12 marker compounds were as follows: 3-caffeoylquinic acid (3-CQA, Lonicerae Flos); CFG and 5-MVS (Saposhnikoviae Radix); liquiritin apioside (LIQA) and glycyrrhizic acid (GA) (Glycyrrhiziae Radix et Rhiza); FA (Cnidia Rhiza); narirutin (NAR), NAG, and NHES (Aurantii Fructus Immaturus); OPDH (Osterici seu Notopterygii Radix et Rhiza); ARC (Forsythiae Fracttus); and 6-gingerol (6-GIN, Zingiberis Rhizo Recens).