Traditional Chinese medicine (TCM) originated in ancient China and has evolved over thousands of years. TCM decoction is the earliest and most widely used form. Different kinds of herbs are mixed together and boiled with water to get decoction, which are usually took by patients themselves. There are some advantages for using decoction, such as effective, absorbed quickly and completely with high bioavailability. However, the decoction is trouble to boil, inconvenient to carry, store and take, which inhibit its clinic application .
The granule of individual herb is called dispensing granule. With the improvement of scientific and technological level, dispensing granules decoction is developed as an alternative to decoctions, prescribed by traditional medicine practitioners in Japan, Korea, Singapore, Hong Kong, Taiwan and Mainland China, or even in the United States and some European countries. Taking Chinese herbal medicine as raw materials, dispensing granules decoction was mainly prepared through extraction, concentration, drying and granulation procedures . It not only has the advantages of the traditional Chinese medicine decoction, but also is convenient to carry, store, and take for patients . Patients could directly mix and dissolve different dispensing granules with hot water in accordance with the recipe of combinatorial formulae to get dispensing granules decoction. However, a debate has continued since the emergence of dispensing granules. The focus of the debate is that the chemical components of dispensing granules decoction may be different from those of traditional decoction, which make their efficacy not equivalent. In fact, a few cases on content changes in marker compounds or chemical consistency during boiling of combinatorial formula have been reported [4–7], which revealed there were differences between dispensing granule decoction and traditional decoction, but no mention of further solution methods.
Modern chromatographic methods such as high performance liquid chromatography (HPLC) using a few compounds as markers have been developed to qualitatively or quantitatively compare the quality of dispensing granule decoction and traditional Chinese medicine decoction [4, 5, 8]. Song-Lin Li  proposed and validated an ultra performance liquid chromatography coupled with photo-diode array detector and time-of-flight mass spectrometry (UPLC-PDA-TOF-MS) based chemical profiling approach to rapidly evaluate chemical consistency between traditional and dispensing granule decoctions of traditional medicine combinatorial formulae using San-Huang-Xie-Xin-Tang (SHXXT) as a model combinatorial formula. In recent years, UPLC-QTOF-MS has been increasingly used for study of many herbs [9–11].
Tao-Hong-Si-Wu decoction is a commonly used traditional combinatorial formula composed of Angelicae Sinensis Radix (Danggui, DG), Chuanxiong Rhizoma (Chuanxiong, CX), Paeoniae Radix Alba (Baishao, BS), Rehmanniae Radix Praeparata (Shudi, SD), Persicae Semen (Taoren, TR) and Carthami Flos (Honghua, HH), which is widely applied in clinical practice for treating primary dysmenorrhea . Tao-Hong-Si-Wu decoction contains many bio-active constituents, such as ferulic acid, senkyunolide I, paeoniflorin, amygdalin, hydroxysafflor yellow A and so on. Ferulic acid, a characteristic aromatic acid in both DG and CH, has been reported that it could significantly improve blood fluidity, inhibit platelet aggregation, decrease serum lipids, prevent thrombus formation, protect neuron like PC12 cells, and exhibit strong antioxidant activity [13–18]. Senkyunolide I, a phthalide in both DG and CX, has been exhibited the activity of reducing the metamorphose damage of the red blood cell caused by ConA . Paeoniflorin, a monoterpene glycoside in BS has been showed many pharmacological effects, such as anticancer, anti-proliferative and neuroprotective [20, 21]. Amygdalin, a quality marker of TR, has been reported to treat asthma, aplastic anemia and tumors in oriental medicine . Hydroxysafflor yellow A, a quality marker of HH, has been demonstrated the activities of antioxidation, myocardial and cerebral protective effects [23–25]. Hydroxysafflor yellow A has also been demonstrated with a strong antagonistic effect on platelet activating factor receptor .
In this paper, chemical consistency between traditional and dispensing granule decoctions of Tao-Hong-Si-Wu decoction was rapidly evaluated by UPLC-QTOF-MS coupled with the MarkerLynx software. Under the chromatographic and MS conditions, the significantly changed components were identified or tentatively assigned by comparing their mass spectrums with the LC-MS/MS library. All the peaks of mass spectrum from Tao-Hong-Si-Wu decoction and each herb were extracted and integration by using QuanLynx™. And the optimized data was used for linear regression analysis. The contribution of each herb in Tao-Hong-Si-Wu decoction, and the optimal compatibility proportion of dispensing granule decoction were derived from the linear regression equation.