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Analysis of Bakuchiol, Psoralen and Angelicin in Crude Drugs and Commercial Concentrated Products of Fructus Psoraleae

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Analysis of Bakuchiol, Psoralen and Angelicin in Crude Drugs and Commercial Concentrated Products of Fructus Psoraleae 433 Journal of Food and Drug Analysis, Vol. 15, No. 4, 2007, Pages 433-437 藥物食品分析 第十五卷 第四期 Analysis of Bakuchiol, Psoralen and Angelicin in Crude Drugs and Commercial Concentrated Products of Fructus Psoraleae CHWAN-FWU LIN1,4, YU-LING HUANG2, MEI-YIN CHIEN3, SHUENN-JYI SHEU1* AND CHIEN-CHIH CHEN2* 1. Department of Chemistry, National Taiwan Normal University, Taipei, Taiwan (R.O.C.) 2. National Research Institute of Chinese Medicine, 155-1, Sec. 2, Li Nung St., Peitou, Taipei, Taiwan (R.O.C.) 3. Ko Da Pharmaceutical Co. Ltd., 20-1, Industrial 3 Rd., Ping-Cheng City, Tao-Yuan, Taiwan (R.O.C.) 4. Department of Cosmetic Science, Chang Gung Institute of Technology, Tao-Yuan, Taiwan (R.O.C.) ABSTRACT The goal of this study was to develop a HPLC method for simultaneously determining bakuchiol, psoralen and angelicin in Fructus Psoraleae (Buguzhi, the fruits of Psoralea corylifolia) and its commercial concentrated products. Extracted samples were analyzed by using a reverse-phase column (Cosmosil 5C18-AR-II) and eluting with a gradient mobile phase consist- ing of 20% acetonitrile to acetonitrile at a flow rate of 1.0 mL/min with detection at a wavelength of 254 nm. The relative standard deviations of the marker substances on the basis of peak-area ratios in intraday and interday analyses were 0.3~1.5% and 0.2~1.0%, respectively. Bakuchiol, psoralen and angelicin contents were 36.2~71.0, 2.5~13.0 and 2.2~9.2 mg/g for ten raw material samples of Fructus Psoraleae, and 0.6~21.1, 0.6~5.2 and 0.6~5.3 mg/g for eight commercial concentrated products of Fructus Psoraleae, respectively. Key words: Psoralea corylifolia, HPLC, bakuchiol, psoralen, angelicin 16 17 INTRODUCTION 18 8 10 5 4 9 5 4 10 11 6 10 6 3 3 12 Psoralea corylifolia L. (Fructus Psoraleae, Chinese 1 11 12 7 2 6 7 2 5 9 O O name Buguzhi) fruits are used in Chinese medicine for 2 O 7 9 O O O 8 4 3 8 HO 13 11 the treatment of premature ejaculation, spermatorrhea, 15 14 12 enuresis, backache, knee pain, pollakiuria, vitiligo, callus, Bakuchiol Psoralen Angelicin psoriasis and alopecia(1). Some coumarins, flavonoids Figure 1. Structures of bakuchiol, psoralen and angelicin. and terpenoids have been isolated from this plant(1-4). Bakuchiol (Figure 1), an important monoterpene phenol, is abundant in the seeds and has been reported to possess DNA polymerase inhibitory activity and show antitumor, concentrated products of Fructus Psoraleae in a single run antibacterial, cytotoxic, anti-helminthic, and anti-oxidant using a reverse phase HPLC method with gradient elution. activities(5-7). Psoralen and angelicin also show anti- bacterial and phototherapeutic activities (Figure 1)(8,9). Although analytical methods for Fructus Psoraleae have MATERIALS AND METHODS been established(10-14), these methods cannot simultaneous- ly quantify these three active compounds. In this study we I. Reagents and Materials isolated three marker substances, i.e. bakuchiol, psoralen, and angelicin, from Fructus Psoraleae and simultaneously Ten batches of the raw material of Fructus Psoraleae measured the contents of these three active compounds were collected from different herbal import companies in raw material of Fructus Psoraleae and the commercial in Taiwan. Eight commercial concentrated products of Fructus Psoraleae were purchased from eight different * Author for correspondence. Shuenn-Jyi Sheu-- factories in Taiwan. Bakuchiol, psoralen and angelicin Tel: +886-2-2935-0749 ext. 405; E-mail: [email protected] Chien-Chih Chen-- Tel: +886-2-2820-1999 ext. 6701; were isolated from Fructus Psoraleae in our laboratory, Fax: +886-2-2826-4276; E-mail: [email protected] and 2-(4-hydroxyphenyl)ethyl alcohol was purchased 434 Journal of Food and Drug Analysis, Vol. 15, No. 4, 2007 from Sigma (St. Louis, MO, USA). Acetonitrile and filtered. The filtrate volume was adjusted to 100 mL with methanol (HPLC grade) were obtained from Mallinckrodt methanol. One milliliter aliquot of the methanolic solu- (Phillipsburg, NJ, USA). Ultra-pure distilled water with tion and 1 mL of internal standard solution [IS, 1 g of 2- a resistivity greater than 18 MΩ was produced by a Milli- (4-hydroxyphenyl)ethyl alcohol in 100 mL MeOH] were Q system (Millipore, Bedford, USA). Samples for HPLC mixed and adjusted to 10 mL with methanol. Five grams were filtered through a 0.45 µm membrane filter (Milli- of commercial concentrated products were treated as pore, Bedford, USA). Melting points were determined pulverized Fructus Psoraleae and diluted with an appro- on a Yanaco MP-I3 micro melting point apparatus. 1H- priate volume of methanol. After filtration (0.45 µm), and 13C-NMR spectra were obtained on a Varian Unity 20 µL of the filtrate was injected into the HPLC system. INOVA 500 or a Bruker AMX-400 NMR spectrometer. Water and 50% methanol were used as extraction solvents EIMS spectra were obtained using a Finnigan MAT GCQ for comparison. spectrometer. IV. Calibration Curves II. Isolation of Marker Substances Stock solutions of bakuchiol, psoralen and angeli- Pulverized Fructus Psoraleae (1.0 kg) was heated for cin were prepared at the concentrations of 175.0, 116.7 2 hr in 5.0 L of Me2CO at 50°C and filtered. The filtrate and 100.0 µg/mL, respectively. The stock solutions were was then condensed under vacuum to give a dry residue. diluted to yield a series of standard solutions with different The residue was chromatographed on a silica gel (70-230 concentrations to construct a calibration curve. To each mesh) column using n-hexane-EtOAc mixture as the of the standard solutions, 1 mL of internal standard solu- eluting solvent. The fraction, eluate of n-hexane-EtOAc tion was added. The calibration curves were prepared by (15:1), was chromatographed on a Sephadex LH-20 plotting the linear regression of the peak-area ratios (y) vs. column (eluting with MeOH) to give bakuchiol (8.5 g). concentrations (x, µg/mL) of each constituent. The eluate of n-hexane-EtOAc (1:1) was repeatedly chro- matographed on silica gel [230-400 mesh, eluting with V. Condition of HPLC Analysis n-hexane-EtOAc (1:1)] and Sephadex LH-20 (eluting with MeOH) to give psoralen (3.2 g) and angelicin (3.4 g). HPLC was conducted on a HP model 1100 system Bakuchiol (1) (17,18) brown liquid; 1H NMR (500 MHz, equipped with a HP G1311A QuatPump, an HP G1322A CDCl3) δ 1.26 (3H, s, H-16), 1.56 (2H, m, H-10), 1.65 (3H, degasser and a HP G1315B photodiode array detector set s, H-15), 1.74 (3H, s, H-14), 2.02 (2H, m, H-11), 5.08 (2H, at 254 nm. The separations involved the use of a reversed m, H-18), 5.17 (1H, br t, H-12), 5.94 (1H, dd, J = 17.3, 10.8 phase column (Cosmosil 5C18-AR-II, 5 µm, 4.6 mm Hz, H-17), 6.11 (1H, d, J = 16.0 Hz, H-8), 6.25 (1H, d, J = I.D. × 250 mm) and a linear gradient from 20% aqueous 16.0 Hz, H-7), 6.82 (2H, d, J = 8.5 Hz, H-3, 5), 7.28 (2H, acetonitrile to 100% acetonitrile for 30 min at a flow rate 13 d, J = 8.5 Hz, H-2, 6); C NMR (125 MHz, CDCl3) δ 17.6 of 1.0 mL/min. (C-15), 23.2 (C-16), 23.3 (C-11), 25.6 (C-14), 41.2 (C-10), 42.4 (C-9), 111.8 (C-18), 115.4 (C-3 and C-5), 124.8 (C-12), VI. Suitability Evaluation 126.4 (C-7), 127.3 (C-2 and C-6), 130.8 (C-1), 131.2 (C- 13), 135.8 (C-8), 145.9 (C-17), 154.5 (C-4); EIMS m/z (rel (I) Reproducibility Test int) 256 (53, [M]+), 241 (15), 213 (50), 186 (23), 173 (100), 158 (16), 145 (71), 107 (24). Standard stock solutions with various concentrations Psoralen (2) (10,16,17) colorless needles from MeOH; mp of bakuchiol (17.5, 35.0 and 175.0 µg/mL), psoralen (1.7, 162-163°C; 1H NMR (400 MHz, CDCl3) δ, 6.37 (1H, d, J 14.5 and 116.7 µg/mL) and angelicin (1.5, 12.5 and 100.0 = 9.6 Hz, H-3), 6.81 (1H, d, J = 2.4 Hz, H-11), 7.46 (1H, s, µg/mL) were used for the reproducibility tests. Intraday H-8), 7.66 (1H, s, H-5), 7.67 (1H, d, J = 2.4 Hz, H-12), 7.79 and interday analyses on precision were performed using (1H, d, J = 9.6 Hz, H-4); EIMS m/z (rel int) 186 (100, [M]+), the optimum HPLC conditions. 158 (53), 130 (12), 102 (14). Angelicin (3) (10,15,17) colorless needles from MeOH; mp (II) Recovery of Bakuchiol, Psoralen, and Angelicin 1 137-138°C; H NMR (400 MHz, CDCl3) δ 6.37 (1H, d, J = 9.6 Hz, H-3), 7.12 (1H, d, J = 2.0 Hz, H-11), 7.36 (1H, d, J = For the accuracy study, three different levels of 8.5 Hz, H-5), 7.42 (1H, d, J = 8.5 Hz, H-6), 7.68 (1H, d, J = bakuchiol (17.5, 35.0 and 70.0 mg), psoralen (5.0, 10.0 2.0 Hz, H-12), 7.79 (1H, d, J = 9.6 Hz, H-4); EIMS m/z (rel and 20.0 mg) and angelicin (5.0, 10.0 and 20.0 mg) were int) 186 (100, [M]+ ), 158 (62), 130 (14), 102 (15).
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