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Journal of Chinese Integrative Medicine ›› 2008, Vol. 6 ›› Issue (11): 1178-1183.doi: 10.3736/jcim20081114

• Original Experimental Research • Previous Articles     Next Articles

Simultaneous determination and pharmacokinetic studies of ferulic acid and paeoniflorin in human serum by high performance liquid chromatography after oral administration of Modified Xiao-yao Decoction

Hui Li1, Ping Ren2, Xi Huang1(), Wen-fu Tang1, Hong-qiang Wei1   

  1. 1. Department of Integrated Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu,Sichuan Province 610041, China
    2. Department of General Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan Province 610041, China
  • Received:2008-05-09 Online:2008-11-20 Published:2008-11-15


To simultaneously determine the contents and explore the pharmacokinetics of ferulic acid and paeoniflorin by high performance liquid chromatography (HPLC) after oral administration of Modified Xiao-yao Decoction (MXYD), a compound of traditional Chinese herbal medicine.


A total of 8 healthy men were enlisted in this study. The serum samples were preprocessed by immersion method. The HPLC system was used to determine the contents of ferulic acid and paeoniflorin in the blood samples of the 8 healthy volunteers, and the blood was collected through the ulnar vein at 5 min, 10 min, 15 min, 30 min, 45 min, 1 h, 2 h and 3 h after MXYD administration. The dates of serum concentration-time were fitted by using the 3P97 analytical program of pharmacokinetics. The internal standard (IS) was coumarin. The detection wavelengths of paeoniflorin and ferulic acid were 230 nm from 0 min to 10 min and 320 nm from 10 min to 25 min respectively.


After MXYD administration, paeoniflorin and ferulic acid were separated completely in the serum and no other interfering peaks were found in the spectrum of the chromatograms. The retention times of the paeoniflorin and ferulic acid were 8.02 min and 13.32 min respectively, and that of the coumarin was 19.14 min. The mean recovery rates of paeoniflorin and ferulic acid were 100.9% and 95.3% with relative standard deviation (RSD) of 3.2% and 3.4%, respectively. The calibration curve for paeoniflorin was linear over the concentration range 40-1 280 ng/ml. Its low-detection limit based on a signal-to-noise ratio of 3 was 5 ng/ml and low-concentration limit was 15 ng/ml with an RSD of 12.5%. Ferulic acid was in the range 10-320 ng/ml; its low-detection limit was 0.65 ng/ml and low-concentration limit was 5 ng/ml with an RSD of 9.7%. The method was found to be highly precise, with an RSD<5% and interday and intraday variability in the range of 92.1%-109.9% for each of the concentrations tested.


This is a study on simultaneously determining paeoniflorin and ferulic acid in serum of healthy volunteers after oral administration of MXYD. The assay is suitable for identifying the serum levels of ferulic acid and paeoniflorin in clinical investigations.

Key words: Jiawei Xiaoyao Powders, paeoniflorin, ferulic acid, high performance liquid chromatography, pharmacokinetics

CLC Number: 

  • R969.1

Figure 1

Typical chromatograms of HPLC for ferulic acid, paeoniflorin and coumarin in serum samples A: Chromatogram of blank serum; B: Chromatogram of serum plus paeoniflorin (peak 1), ferulic acid (peak 2) and coumarin (peak IS); C: Chromatogram of the serum collected at 1 h after oral administration of MXYD, peak 1 is paeoniflorin, peak 2 is ferulic acid, peak IS refers to coumarin."

Figure 2

Ultraviolet spectrograms for blank serum plus paeoniflorin, ferulic acid and coumarin A: Ultraviolet spectrograms of paeoniflorin; B: Ultraviolet spectrograms of ferulic acid; C: Ultraviolet spectrograms of coumarin."

Table 1

Recovery rates of ferulic acid and paeoniflorin in serum"

Component n Nominal
concentration (ng/ml)
rate (x±s, %)
Mean of
recovery rate (%)
RSD (%) Mean of RSD (%)
Ferulic acid 8 10.0 88.6±1.9 95.3 4.2 3.2
8 40.0 98.7±2.4 95.3 2.9 3.2
8 160.0 98.6±2.0 95.3 2.5 3.2
Paeoniflorin 8 40.0 103.4±2.3 100.9 4.9 3.4
8 160.0 99.3±4.1 100.9 3.8 3.4
8 640.0 100.2±3.4 100.9 1.6 3.4

Table 2

Interday variability for ferulic acid and paeoniflorin"

Component n Nominal
concentration (ng/ml)
Measured concentration
(x±s, ng/ml)
Interday variability (%) RSD (%)
Ferulic acid 5 10.0 9.37±0.46 93.7 4.9
5 40.0 40.70±1.81 101.7 4.4
5 160.0 172.77±6.54 100.9 3.8
Paeoniflorin 5 40.0 43.15±1.53 108.0 3.5
5 160.0 160.22±4.89 100.1 3.1
5 640.0 589.24±24.92 92.1 4.2

Table 3

Intraday variability for ferulic acid and paeoniflorin"

Component n Added
concentration (ng/ml)
concentration (x±s, ng/ml)
variability (%)
RSD (%)
Ferulic acid 3 10.0 9.63±0.40 96.3 4.2
3 40.0 41.65±1.56 104.1 3.7
3 160.0 170.42±8.06 106.5 4.7
Paeoniflorin 3 40.0 43.99±1.92 109.9 4.4
3 160.0 158.83±5.24 99.3 3.3
3 640.0 621.81±25.73 97.2 4.1

Figure 3

Serum concentration-time curve of paeoniflorin and ferulic acid after oral administration of MXYD at a dose of 5 g/kg body weight The bars representx±s (n=8)."

Table 4

Pharmacokinetic parameters of ferulic acid and paeoniflorin in serum"

Component n Tmax
(x±s, min)
(x±s, min)
[x±s, L/(min·kg)]
AUC(0-3 min)
[x±s, μg/(L·h)]
MRT(0-3 min)
(x±s, min)
Ferulic acid 8 45.00±11.34 70.81±7.17 33.39±20.80 714.399±187.451 6 434.77±1 192.56 66.910±10.461
Paeoniflorin 8 43.13±9.61 536.08±49.03 55.70±25.26 66.310±24.606 71 639.31±16 625.00 121.200±17.242
[1] Yu GH, Liang SC, Sun QZ , et al. Study on modified Xiaoyao Decoction combining clomipamine in treating depression[J]. Zhongguo Zhong Xi Yi Jie He Za Zhi, 2007,27(4):318-320
余国汉, 梁绍财, 孙祺章 , 等. 加味逍遥汤合并氯米帕明治疗抑郁症的对照研究[J]. 中国中西医结合杂志, 2007,27(4):318-320
[2] Ren P, Huang X, Li SQ , et al. Effect of modified Xiaoyao powder on electrogastrographic picture and pharmacokinetic characteristics of ferulic acid in patients with functional dyspepsia of Gan-qi stagnation with Pi-deficiency syndrome type[J]. Zhongguo Zhong Xi Yi Jie He Za Zhi, 2006,26(5):398-402
任平, 黄熙, 李双庆 , 等. 加味逍遥散对功能性消化不良肝郁脾虚型患者胃电图及阿魏酸药动学特征的影响[J]. 中国中西医结合杂志, 2006,26(5):398-402
[3] Yang YX, Huang X, Ren P , et al. HPLC determination of concentration of ferulic acid in blood of patients with liver depression and spleen deficiency[J]. Nanjing Zhong Yi Yao Da Xue Xue Bao, 2003,19(2):86-88
杨玉兴, 黄熙, 任平 , 等. 肝郁脾虚证患者口服加味逍遥散后阿魏酸的血药浓度HPLC测定法[J]. 南京中医药大学学报, 2003,19(2):86-88
[4] Yang XG, Peng B, Zhang GH , et al.Studies of the pharmacokinetics of paeoniflorin in two Jing-Zhi-Guan-Xin formulations after oral administration to beagle dogs[J].J Pharm Biomed Anal, 2006, 41: 320-324
doi: 10.1016/j.jpba.2005.11.004
[5] Luo HM, Li XG, Xiao F , et al. Study on pharmacokinetics of ferulic acid and paeoniflorin in Angelic-Paeonia Root Powder[J]. Zhong Yao Cai, 2003,26(3):189-192
doi: 10.3321/j.issn:1001-4454.2003.03.017
罗焕敏, 李晓光, 肖飞 . 当归芍药散中阿魏酸和芍药苷的药代动力学研究[J]. 中药材, 2003,26(3):189-192
doi: 10.3321/j.issn:1001-4454.2003.03.017
[6] Xu S, Hu JH . Determination of sodium ferulate in Beagle dog serum by HPLC and its pharmacokinetics[J]. Zhong Cheng Yao, 2005,9(27):1062-1065
徐术, 胡晋红 . HPLC测定Beagle犬血浆中阿魏酸钠的浓度及药动学研究[J]. 中成药, 2005,9(27):1062-1065
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