A Method for Quantitative Determination of Furanocoumarins in Capsules and Tablets of Phytochemical Preparations

Abstract

Furanocoumarins are known as photoreactive compounds and are increasingly used for photochemotherapic dermatologic treatments of diseases such as vitiligo, psoriasis, mycosis fungoides, atopic eczema and alopecia areata, among others.1,2) The furanocoumarins have been used in some pharmaceutical and cosmetic products because of their UV light absorbing properties.3) In photochemotherapy psoralens are often employed orally or topically, associated with Ultraviolet A (UVA) irradiation. The combination of these cited compounds with UVA irradiation is known as PUVA therapy (psoralens plus UVA irradiation). 4-7)The biological activity of these compounds is attributable to their ability to intercalate into DNA, where they are able to form monoadducts and crosslinks in the presence of longwave UV light. 8) On the other hand, use of psoralens in medicine has been associated with higher incidence of skin cancer, [8][9][10] and several studies have demonstrated that the psoralens are carcinogenic, mutagenic and photodermatitic. 11,12) Linear psoralens cause phototoxicity. 13,14) Usually, the amount of the compounds psoralen and bergapten is used as an index of the phototoxic activity of a plant. 15) In preliminary analysis psoralen, bergaten and 5benzopyran-7-one were identified in samples analyzed in this study. The capsules and tablets employed are indicated, according to their technical information, for the treatment of menstrual irregularities, abdominal and menstrual cramps, vaginal discharge, daily pre-menstrual tension, disturbances related to the menopause, inflammations of the lymphatic nodes or vitiligo.For most of the phytomedicines used in Brazil there is no information on their exact composition in relation to the substances they contain or on the recommended dosages, imposing serious risks to public health. The samples analyzed showed the presence of Dorstenia species and other plants. Dorstenia species are known for their ability to synthesize linear and angular furanocoumarins. 15) HPLC equipment is widely disseminated in Brazil. We have developed an analytical procedure suitable for sample preparation and HPLC-UV analysis of the three furanocoumarins mentioned earlier in phytomedicines (capsules and tablets). The HPLC technique has been shown to be a very efficient system for separating complex mixtures like phytomedicines. HPLC methods have been reported for the determination of psoralens in callus cultures, vitro culture, serum, dermis, plants, citrus, essential oils and phytomedicines, but only the most recent published methods report assay validation.6,15-24) Liquid and gas chromatographic methods have shown the determination of furanocoumarins in phytomedicines, 15,25) however, there are no descriptions in the literature about sample preparation or analysis of psoralen (P), bergapten (G) or 5-[3-(4,5-dihydro-5,5-dimethyl-4-oxo-2-furanyl)-butoxy]-7H-furo[3-2-g][1]benzopyran-7-one (DT) (Fig. 1) present in phytochemical preparations (capsules and tablets) employed in Brazil.The validation of the procedu...

Simultaneous determination of five coumarins in Angelicae dahuricae Radix by HPLC/UV and LC‐ESI‐MS/MS

“…Thus, the established methods have the potential to be used for the quality control of Angelicae dahuricae Radix extracts and its pharmaceutical preparations. The HPLC analysis of coumarins is already reported (Cardoso et al, 2006), but this is the first report regarding simultaneous determination of the five coumarins, byakangelicol, oxypeucedanin, imperatorin, phellopterin and isoimperatorin, to the best of our knowledge. In addition, we could achieve the baseline separation of the five coumarins using a C 30 column.…”

Comparison of citrus coumarins on carcinogen-detoxifying enzymes in Nrf2 knockout mice

“…Isopimpinellin, which is present in celery, limes, and Angelica -containing traditional Chinese medicine, appears to possess different properties than imperatorin, which is found in lemons and also in Angelica-containing traditional Chinese medicine (Beier et al, 1983; Cardoso et al, 2006; Frerot and Decorzant, 2004; Ivie and Beier, 1996). These two linear furanocoumarins differ by the substitutions across the center ring, with isopimpinellin containing two methoxy groups, and imperatorin possessing one allyloxy group.…”

Effects of naturally occurring coumarins on hepatic drug-metabolizing enzymes inmice

“…NOCs are also present as Crude Drugs in Traditional Chinese Medicine and other phytomedicines. Human exposure to furanocoumarins following consumption of tablets prepared from Dorstenia species in Brazil was estimated to be 2–5.36 mg/d (Cardoso et al , 2006). Concentrations of imperatorin and isoimperatorin were reported to be 40–60 μg/mL and 12–44 μg/mL (respectively) in the Crude Drug Radix Angelica Dahurica (Cardoso et al ., 2006).…”

“…Human exposure to furanocoumarins following consumption of tablets prepared from Dorstenia species in Brazil was estimated to be 2–5.36 mg/d (Cardoso et al , 2006). Concentrations of imperatorin and isoimperatorin were reported to be 40–60 μg/mL and 12–44 μg/mL (respectively) in the Crude Drug Radix Angelica Dahurica (Cardoso et al ., 2006). Several coumarins, including 7-hydroxycoumarin, 7-methoxycoumarin, 5,7-dimethoxycoumarin (limettin), 5-methoxypsoralen, 8-methoxypsoralen, and 5,8-dimethoxypsoralen (isopimpinellin) were detected by LC-UV in human urine following ingestion of Umbelliferae Chinese herbal medicine (Wang and Jiang, 2006).…”