Efficient Separation of the Methoxyfuranocoumarins Peucedanin, 8-Methoxypeucedanin, and Bergapten by Centrifugal Partition Chromatography (CPC).

Pure methoxyfuranocoumarins were isolated from a crude petroleum ether extract (CPE; Soxleth extraction efficiency 12.28%) from fruits of Peucedanum tauricum MB. (Apiaceae) by counter-current chromatography in a hydrostatic equilibrium system (centrifugal partition chromatography-CPC). The optimized biphasic solvent system composed of n-heptane-ethyl acetate-methanol-water (5:2:5:2; v/v/v/v) in the ascending mode of elution was used (3 mL/min, 1600 rpm). In the single run, peucedanin (P), 8-methoxypeucedanin (8MP), and bergapten (5MOP) were obtained as pure as 95.6%, 98.1%, and c.a. 100%, respectively. The carefully optimized and developed CPC was effectively transferred from the analytical to the semi-preparative scale (where 20 mg and 150 mg of CPE were loaded, respectively). Identification and quantitative analysis of methoxyfuranocoumarins was carried out in the plant material, in the CPE, and in individual CPC fractions by use of validated high-performance liquid chromatography with diode array detection and mass spectrometry (HPLC-DAD-ESI-MS). For the separation steps, the extraction/isolation recovery was calculated. In this case, CPC proved to be an effective tool for the simultaneous isolation and separation of P, 8MP, and 5MOP from a multicomponent plant matrix, without additional pre-purification steps. The high purity of the obtained plant metabolites makes it possible to consider their use in pharmacological or biological studies.

[Quality evaluation of Psoraleae Fructus based on QAMS method and TLC identification].

The present study established a determination method of Psoraleae Fructus by quantitative analysis of multi-components by the single marker(QAMS) and further improved the thin-layer chromatography(TLC) method. The QAMS method was established by UPLC with psoralen as the internal marker, and the content of psoralenoside, isopsoralenoside, psoralen, and isopsoralen was simultaneously determined. As revealed by the comparison with results of the external standard method, the QAMS method was accurate and feasible. According to the current quality standards of Psoraleae Fructus, the TLC method was further optimized and improved, and bakuchiol was added for identification based on the original TLC method with psoralen and isopsoralen as indicators. This study provides a reference for improving the quality control method of Psoraleae Fructus.

Simultaneous separation and determination of six furanocoumarins in Radix Angelicae dahuricae by CZE with dual CDs system.

A novel, simple and efficient capillary electrophoresis method was developed to simultaneous determination of six furanocoumarins (psoralen, isopsoralen, imperatorin, isoimperatorin, phellopterin, and cnidilin). The separation buffer consisted of 30 mM boric acid, 12 mM sulfobutylether-ß-cyclodextrin and 1.5 mM 2-hydroxypropyl-ß-cyclodextrin (pH 7.8); the voltage was 20 kV, the temperature was 25 °C and the detection wavelength was at 246 nm with a diode array detector (DAD). Under the above conditions, the analytes could be separated with high resolution in less than 7 min. This method was used to simultaneously determine the content of psoralen, imperatorin, isoimperatorin and phellopterin in Angelica Dahurica Radix. And good linearities were obtained with correlation coefficients from 0.9992 to 0.9999. The limits of detection (LOD, S/N = 3) and the limits of quantitation (LOQ, S/N = 10) ranged from 0.6 to 3.0 µg/mL and from 2.1 to 9.9 µg/mL, respectively. The recoveries ranged between 98.8% and 101.8%. The results indicated the method can achieve baseline separation and quantitative analysis of furanocoumarins in Chinese herbal medicines and formulations.

[Pharmacokinetic characteristics of psoralen,isopsoralen,psoralenoside and isopsoralenoside in rats after oral administration of Psoraleae Fructus extract].

Coumarins are the main active components in Psoraleae Fructus. To study the multi-component pharmacokinetics of Psoraleae Fructus, this study established a sensitive and rapid ultra-pressure liquid chromatography coupled to tandem mass spectrometry(UPLC-MS/MS) method for simultaneous determination of psoralen, isopsoralen, psoralenoside, and isopsoralenoside in rat plasma. After validation, the method was applied to the investigation of pharmacokinetics of psoralen, isopsoralen, psoralenoside, and isopso-ralenoside in rats after single and multiple administration of Psoraleae Fructus extract. The results revealed that the exposure of psoralen and isopsoralen in rat plasma was high after a single intragastric administration of Psoraleae Fructus extract, with an AUC_(0-∞) of 443 619-582 680 and 167 314-276 903 ng·mL~(-1)·h~(-1), respectively. Compared with these two compounds, the exposure of psoralenoside and isopsoralenoside was lower with marked gender difference. After 7-day administration of Psoraleae Fructus extract to rats, the AUC_(0-∞) of psoralen and isopsoralen was 29 701-81 783 and 39 234-89 914 ng·mL~(-1)·h~(-1), respectively, which was significantly lower than that at the first day(P<0.05), and that of psoralenoside and isopsoralenoside was 7 360-19 342 and 8 823-45 501 ng·mL~(-1)·h~(-1), respectively. There was no significant gender difference in exposure of psoralenoside and isopsoralenoside in male and female rats. However, the exposure of psoralenoside and isopsoralenoside in male rats was reduced(P<0.05), and the t_(1/2) and mean residence time(MRT) were shortened, suggesting that the removal of these two compounds from the body was accelerated.

Isolation of secondary metabolites from the Iranian medicinal plant Eremurus persicus.

Eremurus persicus (Jaub. & Spach) Boiss. belonging to Xanthorrhoeaceae family is an endemic medicinal plant widely distributed in Iran. Its leaves have been traditionally used as a food and also as medicinal plant. Regarding the widespread application of E. persicus in Iranian folk medicine, and the insignificant investigation of its components, this study aimed at the isolation and identification of major secondary metabolites of this plant. By applying various chromatographic techniques, corchoionoside A (1), 4-amino-4-carboxychroman-2-one (2), isoorientin (3), ziganein 5-methyl ether (4), auraptene (5), and imperatorin (6) were isolated from the EtOAc and CHCl3 fractions of the crude extract. Except isoorientin (3), all the identified phytoconstituents were reported for the first time from Eremurus genus.

Pharmacokinetic characteristics of psoralen,isopsoralen,psoralenoside and isopsoralenoside in rats after oral administration of Psoraleae Fructus extract / 中国中药杂志

Coumarins are the main active components in Psoraleae Fructus. To study the multi-component pharmacokinetics of Psoraleae Fructus, this study established a sensitive and rapid ultra-pressure liquid chromatography coupled to tandem mass spectrometry(UPLC-MS/MS) method for simultaneous determination of psoralen, isopsoralen, psoralenoside, and isopsoralenoside in rat plasma. After validation, the method was applied to the investigation of pharmacokinetics of psoralen, isopsoralen, psoralenoside, and isopso-ralenoside in rats after single and multiple administration of Psoraleae Fructus extract. The results revealed that the exposure of psoralen and isopsoralen in rat plasma was high after a single intragastric administration of Psoraleae Fructus extract, with an AUC_(0-∞) of 443 619-582 680 and 167 314-276 903 ng·mL~(-1)·h~(-1), respectively. Compared with these two compounds, the exposure of psoralenoside and isopsoralenoside was lower with marked gender difference. After 7-day administration of Psoraleae Fructus extract to rats, the AUC_(0-∞) of psoralen and isopsoralen was 29 701-81 783 and 39 234-89 914 ng·mL~(-1)·h~(-1), respectively, which was significantly lower than that at the first day(P<0.05), and that of psoralenoside and isopsoralenoside was 7 360-19 342 and 8 823-45 501 ng·mL~(-1)·h~(-1), respectively. There was no significant gender difference in exposure of psoralenoside and isopsoralenoside in male and female rats. However, the exposure of psoralenoside and isopsoralenoside in male rats was reduced(P<0.05), and the t_(1/2) and mean residence time(MRT) were shortened, suggesting that the removal of these two compounds from the body was accelerated.

[Quantitative determination of nine furanocoumarins for quality evaluation of Angelica dahurica from different habitats].

A UPLC method has been developed for simultaneous determination of nine furanocoumarins of Angelica dahurics,and was used for quality evaluation of A. dahurica from different habitats. ACQUITY UPLC BEH C18 chromatographic column was employed,the separation was performed with the mobile phase consisting of acetonitrile and water,and the detection wavelength was set at254 nm. This method was used to simultaneously determine the content of xanthotoxol,oxypeucedaninhydrate,byak-angelicin,psoralen,xanthotoxin,bergapten,oxypeucedanin,imperatorin and isoimperatorin in A. dahurica from different habitats. Then,the further quality assessment of the drug was carried out by similarity evaluation,cluster analysis( CA),principal component analysis( PCA),and orthogonal partial least squares discriminant analysis( OPLS-DA). The content order of measured furanocoumarins from high to low was: oxypeucedanin>imperatorin>isoimperatorin>oxypeucedaninhydrate>bergapten>byak-angelicin>xanthotoxin>xanthotoxol>psoralen,with the mean content 2. 844,1. 277,0. 649 2,0. 216 2,0. 129 8,0. 062 68,0. 052 68,0. 019 30,0. 018 19 mg·g-1,respectively. There were difference between the batches of the drug,and the quality was influenced by smouldering sulphur based on the results of chemical pattern recognition and content determination. Finally,six active ingredients were recognized as the quality makers using OPLS-DA method. The validated UPLC fingerprint combined with chemical pattern recognition method can be used in the quality control and evaluation of A. dahurica.

Evaluation of the Absorption Behavior of Main Component Compounds of Salt-Fried Herb Ingredients in Qing'e Pills by Using Caco-2 Cell Model.

Qing'e Pills is a Chinese traditional herbal product, which is often used to strengthen muscles and bones in TCM (traditional Chinese Medicine) practice. Its two main component herbs, namely, Cortex Eucommiae and Fructus Psoraleae are both required to be salt-fried according to TCM theory. We have evaluated the effects of salt-frying treated herbs on Caco-2 cell uptake behavior for those active ingredients of Qing'e Pills. By investigating of various variables, including MTT, temperature, inhibitors, pH, salt concentration and herb processing methods, we tried to clarify whether the salt-processing on herbs was necessary or not. Results showed that, compared to other processing methods, the salt-frying process significantly (p < 0.01) enhanced the absorption of effective components of Qing'e Pills. The way that psoralen, isopsoralen, psoralenoside and geniposide acid entered Caco-2 cells at low concentrations was via passive diffusion. These components were not substrates of P-glycoprotein. It demonstrated that the salt-frying process not only enhanced the concentration of active components in herb extract, but also changed their absorption behaviors. Nevertheless, the mechanism of absorption behavior changing needs to be further investigated.

The comparative pharmacokinetic study of Yuanhu Zhitong prescription based on five quality-markers.

BACKGROUND: According to the compatibility theory, therapeutic effects of Chinese medicine prescription are generally attributed to the synergism of multi-herbs. Quality-markers, as the crucial effective components, play a key role in the interaction of compatibility. Pharmacokinetic studies could illustrate the interaction between multiple components in dynamics perspective. PURPOSE: This study aims to establish a rapid, reliable and sensitive ultra performance liquid chromatography coupled with tandem mass spectrometry method for simultaneous determination of corydaline, tetrahydropalmatine, protopine, imperatorin and isoimperatorin (quality-markers of Yuanhu Zhitong prescription) in rat plasma, and then applied to the comparative pharmacokinetic study for clearing the interaction of compatibility in Yuanhu Zhitong prescription. METHODS: Five quality-markers were separated on a Waters Acquity UPLC BEH C18 column (2.1 mm × 50 mm, 1.7 µm) by gradient elution with 0.1% formic acid-water and 0.1% formic acid-acetonitrile. Detection was performed in the positive ionization and multiple reaction monitoring mode. The analytical method was validated and successfully applied to the comparative pharmacokinetic study after oral administration of Yuanhu Zhitong prescription and single-herb extracts. RESULTS: Calibration curves showed good linearity over the concentration ranges of 0.25-500 ng/ml for corydaline, tetrahydropalmatine and isoimperatorin, 0.1-200 ng/ml for protopine, and 0.5-500 ng/ml for imperatorin, respectively. Compared with Rhizoma corydalis group, AUC0-t and AUC0-∞ significantly increased (p < 0.01 for corydaline and tetrahydropalmatine, and p < 0.05 for protopine) after oral administration of Yuanhu Zhitong prescription extract. Meanwhile, Cmax of corydaline and tetrahydropalmatine increased remarkably, from 93.00 µg/l to 196.35 µg/l for corydaline (p < 0.05) and 181.62 µg/l to 311.22 µg/l for tetrahydropalmatine (p < 0.01). In addition, MRT0-t and MRT0-∞ of corydaline, as well as Tmax of protopine in Yuanhu Zhitong prescription group were obviously delayed compared to Rhizoma corydalis group (p < 0.01). CONCLUSION: These achieved results indicated that the compatibility of Rhizoma corydalis and Radix Angelicae dahuricae lead to greater absorption of corydaline, tetrahydropalmatine and protopine, which would be help to better understand the compatibility mechanism of Yuanhu Zhitong prescription.

Identification of quality markers of Yuanhu Zhitong tablets based on integrative pharmacology and data mining.

BACKGROUND: The quality evaluation of traditional Chinese medicine (TCM) formulations is needed to guarantee the safety and efficacy. In our laboratory, we established interaction rules between chemical quality control and biological activity evaluations to study Yuanhu Zhitong tablets (YZTs). Moreover, a quality marker (Q-marker) has recently been proposed as a new concept in the quality control of TCM. However, no appropriate methods are available for the identification of Q-markers from the complex TCM systems. PURPOSE: We aimed to use an integrative pharmacological (IP) approach to further identify Q-markers from YZTs through the integration of multidisciplinary knowledge. In addition, data mining was used to determine the correlation between multiple constituents of this TCM and its bioactivity to improve quality control. METHODS: The IP approach was used to identify the active constituents of YZTs and elucidate the molecular mechanisms by integrating chemical and biosynthetic analyses, drug metabolism, and network pharmacology. Data mining methods including grey relational analysis (GRA) and least squares support vector machine (LS-SVM) regression techniques, were used to establish the correlations among the constituents and efficacy, and dose efficacy in multiple dimensions. RESULTS: Seven constituents (tetrahydropalmatine, α-allocryptopine, protopine, corydaline, imperatorin, isoimperatorin, and byakangelicin) were identified as Q-markers of YZT using IP based on their high abundance, specific presence in the individual herbal constituents and the product, appropriate drug-like properties, and critical contribution to the bioactivity of the mixture of YZT constituents. Moreover, three Q-markers (protopine, α-allocryptopine, and corydaline) were highly correlated with the multiple bioactivities of the YZTs, as found using data mining. Finally, three constituents (tetrahydropalmatine, corydaline, and imperatorin) were chosen as minimum combinations that both distinguished the authentic components from false products and indicated the intensity of bioactivity to improve the quality control of YZTs. CONCLUSIONS: Tetrahydropalmatine, imperatorin, and corydaline could be used as minimum combinations to effectively control the quality of YZTs.

A Method for LC-MS/MS Profiling of Coumarins in Zanthoxylum zanthoxyloides (Lam.) B. Zepernich and Timler Extracts and Essential Oils.

The metabolites from the coumarin class, present in tissues of plants belonging mainly to the Rutaceae and Apiaceae families, included compounds with high chemical diversity such as simple coumarins and furocoumarins. These health-promoting components are recognized for their valuable biological activities in herbal preparations but also for their phototoxic effects. In this work, a targeted liquid chromatography (LC) coupled with tandem mass spectrometry (MS²) was developed for the screening of 39 reference standards of coumarins and furocoumarins in essential oils and plant extracts. Chromatographic separation was accomplished on reversed phase column using water/acetonitrile as the mobile phase and detection was performed on a hybrid QqQ/linear ion trap spectrometer fitted with an atmospheric pressure chemical ionization (APCI) source operating in positive ion mode. This analytical approach was applied to investigate the coumarin compositions of fruit essential oils and methanolic extracts obtained from separated parts (fruit, leaf, stem, trunk, and root) of Zanthoxylum zanthoxyloides. Ten coumarins and six furanocoumarins were reported in this species and data analyses were used to assess the suitability of these compounds to the metabolomics-based differentiation of plant organs. The quantification criteria of the metabolites in extract samples included linearity, limit of quantification, limit of detection, and matrix effect were validated. As reported for other species of the Rutaceae family, the concentration of coumarins was drastically higher in Z. zanthoxyloides fruits than in other plant organs.

Investigations on the constituents of SagaPro tablets, a food supplement manufactured from Angelica archangelica leaf.

Saga Pro is a food supplement product manufactured in Iceland and marketed internationally. It is claimed to have anti-nocturia effect and the flavonoid isoquercitrin has been suggested to play a role in this assumed activity. The purpose of this study was to identify and quantify the main flavonoids and furanocoumarins in the SagaPro tablets and to evaluate the importance of their presence. Isoquercitrin was identified as a constituent in an amount of 158 µg/tablet. This is a p.o. dosage highly unlikely to have an effect on nocturia or any other pharmacologically significant effect in humans. The main furanocoumarins, xanthotoxin and imperatorin, were also identified and quantified to 280 and 2 µg/tablet, respectively.

Direct Analysis in Real-time Mass Spectrometry for Rapid Identification of Traditional Chinese Medicines with Coumarins as Primary Characteristics.

INTRODUCTION: The increasing popularity of traditional Chinese medicines (TCMs) necessitates rapid and reliable methods for controlling their quality. Direct analysis in real-time mass spectrometry (DART-MS) represents a novel approach to analysing TCMs. OBJECTIVE: To develop a quick and reliable method of identifying TCMs with coumarins as primary characteristics. METHODOLOGY: DART-MS coupled with ion trap mass spectrometry was employed to rapidly identify TCMs with coumarins as primary characteristics and to explore the ionisation mechanisms of simple coumarins, furocoumarins and pyranocoumarins in detail. With minimal sample pretreatment, mass spectra of Fraxini Cortex, Angelicae Pubescentis Radix, Peucedani Radix and Psoraleae Fructus samples were obtained within seconds. The operating parameters of the DART ion source (e.g. grid electrode voltage and ionisation gas temperature) were carefully investigated to obtain high-quality mass spectra. The mass spectra of samples and DART-MS/MS spectra of marker compounds were used to identify sample materials. RESULTS: Successful authentication was achieved by analysing the same materials of different origins. Some simple coumarins, furocoumarins and pyranocoumarins can be directly detected by DART-MS as marker compounds. CONCLUSION: Our results demonstrated that DART-MS can provide a rapid and reliable method for the identification of TCMs containing different configurations of coumarins; the method may also be applicable to other plants. Copyright © 2016 John Wiley & Sons, Ltd.

[Effect investigation of coumarin constituents in Angelica dahurica on pharmacokinetics of docetaxel by LC-MS].

The study was aimed to establish a liquid chromatography-tandem mass spectrometric method for the determination of the docetaxel concentration in rat plasma, and study the effect of coumarin constituents (imperatorin, isoimperatorin and oxypeucedanin) in Angelica dahurica on pharmacokinetics of docetaxel.Plasma was precipitated with acetonitrile and determined by LC-MS method with Paclitaxel as an internal standard. The specificity, linearity, range, accuracy, precision and stability of the method were suitable for the determination of docetaxel in plasma.Six sprague-dawley rats in each group received intragastric administration of docetaxel (50 mg•kg⁻¹), oxypeucedanin (8 mg•kg⁻¹) combined with docetaxel (50 mg•kg⁻¹), imperatorin (15 mg•kg⁻¹) combined with docetaxel (50 mg•kg⁻¹), and isoimperatorin(15 mg•kg⁻¹) combined with docetaxel (50 mg•kg⁻¹).Their drug plasma concentration was determined by LC-MS with Paclitaxel as an internal standard to draw plasma concentration-time curve, and the phamacokinetic parameters were calculated by DAS 2.0. The results showed that the phamacokinetic parameters of docetaxel all had notable changes when combined with imperatorin, isoimperatorin, and oxypeucedanin, respectively. The phamacokinetic parameters AUC and Cmax were significantly increased, indicating that coumarin constituents in Angelica dahurica could promote the oral bioavailability of docetaxel, and their effects were in the following order: oxypeucedanin> isoimperatorin> imperatorin.

Variation in Key Flavonoid Biosynthetic Enzymes and Phytochemicals in 'Rio Red' Grapefruit (Citrus paradisi Macf.) during Fruit Development.

In the current study, the phytochemical contents and expression of genes involved in flavonoid biosynthesis in Rio Red grapefruit were studied at different developmental and maturity stages for the first time. Grapefruit were harvested in June, August, November, January, and April and analyzed for the levels of carotenoids, vitamin C, limonoids, flavonoids, and furocoumarins by HPLC. In addition, genes encoding for phenylalanine ammonia-lyase (PAL), chalcone synthase (CHS), chalcone isomerase (CHI), and 1,2-rhamnosyltransferase (2RT) were isolated, and their expression in grapefruit juice vesicles was studied. Fruit maturity had significant influence on the expression of the genes, with PAL, CHS, and CHI having higher expression in immature fruits (June), whereas 2RT expression was higher in mature fruits (November and January). The levels of flavonoids (except naringin and poncirin), vitamin C, and furocoumarins gradually decreased from June to April. Furthermore, limonin levels sharply decreased in January. Lycopene decreased whereas ß-carotene gradually increased with fruit maturity. Naringin did not exactly follow the pattern of 2RT or of PAL, CHS, and CHI expression, indicating that the four genes may have complementary effects on the level of naringin. Nevertheless, of the marketable fruit stages, early-season grapefruits harvested in November contained more beneficial phytochemicals as compared to mid- and late-season fruits harvested in January and April, respectively.

A pre-classification strategy based on UPLC-Triple-TOF/MS for metabolic screening and identification of Radix glehniae in rats.

Traditional Chinese Medicines (TCMs) have gained increasing popularity in modern society. However, the profiles of TCMs in vivo are still unclear owing to their complexity and low level in vivo. In this study, UPLC-Triple-TOF techniques were employed for data acquiring, and a novel pre-classification strategy was developed to rapidly and systematically screen and identify the absorbed constituents and metabolites of TCMs in vivo using Radix glehniae as the research object. In this strategy, pre-classification for absorbed constituents was first performed according to the similarity of their structures. Then representative constituents were elected from every class and analyzed separately to screen non-target absorbed constituents and metabolites in biosamples. This pre-classification strategy is basing on target (known) constituents to screen non-target (unknown) constituents from the massive data acquired by mass spectrometry. Finally, the screened candidate compounds were interpreted and identified based on a predicted metabolic pathway, well - studied fragmentation rules, a predicted metabolic pathway, polarity and retention time of the compounds, and some related literature. With this method, a total of 111 absorbed constituents and metabolites of Radix glehniae in rats' urine, plasma, and bile samples were screened and identified or tentatively characterized successfully. This strategy provides an idea for the screening and identification of the metabolites of other TCMs.

UPLC-QTOF-MS/MS based screening and identification of the metabolites in rat bile after oral administration of imperatorin.

The detection of drug metabolites, particularly for minor metabolites, continues to be a challenge owing to the complexity of biological samples. Imperatorin is an active natural furocoumarin ingredient originating from many traditional Chinese herbal medicines. In the present study, the metabolites of imperatorin after oral administration were qualitatively investigated, and possible metabolic pathways of it were subsequently proposed. Bile samples were collected after oral administration and pretreated by the application of Waters Ostro. The QTOF-MS/MS data was acquired using ultra high performance liquid chromatography coupled to quadrupole time flight spectrometry (UPLC-QTOF-MS). Based on this analytical strategy, 32 metabolites (23 phase I and 9 phase II metabolites) were identified in rat bile. The results demonstrated that C5H8 could be easily eliminated from imperatorin forming the metabolite M1. It also indicated that imperatorin and M1 underwent extensive metabolic reactions including oxidation, hydrolysis, methylation, glucuronide conjugation, C2H5NO2S conjugation and C3H5NO2S conjugation. This is the first study of imperatorin metabolism in bile samples. The proposed metabolic pathways in this research will provide essential data for further pharmaceutical studies of other linear-type furocoumarins.

A new phenolic glycoside and two new monoterpenoid furocoumarins from Aurantii Fructus Immaturus.

A new phenolic glycoside, citrauranoside A (1), and two new monoterpenoid furocoumarins, citraurancoumarin A (2) and citraurancoumarin B (3), along with four known compounds (4-7) were isolated from the young fruit of Citrus aurantium L. The structures were elucidated by their comprehensive analysis including 1D, 2DNMR, IR and mass spectra.

[Correspondence analysis between traditional commercial specifications and quantitative quality indices of Notopterygii Rhizoma et Radix].

This paper aims to explore a comprehensive assessment method combined traditional Chinese medicinal material specifications with quantitative quality indicators. Seventy-six samples of Notopterygii Rhizoma et Radix were collected on market and at producing areas. Traditional commercial specifications were described and assigned, and 10 chemical components and volatile oils were determined for each sample. Cluster analysis, Fisher discriminant analysis and correspondence analysis were used to establish the relationship between the traditional qualitative commercial specifications and quantitative chemical indices for comprehensive evaluating quality of medicinal materials, and quantitative classification of commercial grade and quality grade. A herb quality index (HQI) including traditional commercial specifications and chemical components for quantitative grade classification were established, and corresponding discriminant function were figured out for precise determination of quality grade and sub-grade of Notopterygii Rhizoma et Radix. The result showed that notopterol, isoimperatorin and volatile oil were the major components for determination of chemical quality, and their dividing values were specified for every grade and sub-grade of the commercial materials of Notopterygii Rhizoma et Radix. According to the result, essential relationship between traditional medicinal indicators, qualitative commercial specifications, and quantitative chemical composition indicators can be examined by K-mean cluster, Fisher discriminant analysis and correspondence analysis, which provide a new method for comprehensive quantitative evaluation of traditional Chinese medicine quality integrated traditional commodity specifications and quantitative modern chemical index.

Separation and simultaneous quantification of nine furanocoumarins from Radix Angelicae dahuricae using liquid chromatography with tandem mass spectrometry for bioavailability determination in rats.

Radix Angelicae dahuricae is a well-known medicinal herb in a number of herb preparations for medical uses. In this study, a rapid and selective method using liquid chromatography with tandem mass spectrometry was developed for the separation and simultaneous quantitation of nine furanocoumarins from Radix A. dahuricae, namely imperatorin, isoimperatorin, oxypeucedanin hydrate, bergapten, oxypeucedanin, xanthotoxol, xanthotoxin, isopimpinellin, and psoralen. Chromatographic separation was achieved on a CAPCELL PAK MG II C18 analytical column. Detection was performed using positive electrospray ion source in the multiple reaction monitoring mode. The method was fully validated for analyzing these principles in rat plasma with a lower limit of quantification from 0.5 to 5 ng/mL. The intra- and interbatch precisions were less than 10%, and the accuracies ranged from -7.5 to 8.0%. The extraction recovery of the analytes was above 70% without a significant matrix effect. The method was used to determine the oral and intravenous pharmacokinetic profiles of these furanocoumarins after dosing with Radix A. dahurica extract. The bioavailability of these furanocoumarins ranged from 10.1 to 82.8%. These data provide critical information for a better understanding of the pharmacological mechanisms and herb-drug interaction potential of Radix A. dahurica.