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Liquid chromatography with quadrupole time-of-flight mass spectrometry coupled with automated data analysis by Peakview software was employed to systematically screen and characterize the astragalosides in Radix Astragali, a Chinese medical preparation. The separation was performed on a poroshell 120 SB-C18 column equipped in a conventional liquid chromatography system. After being separated using a general gradient elution, the analytes were detected by the triple quadrupole time-of-flight mass spectrometer in both positive- and negative-ion modes. The mass defect filtering function built in the Peakview software was utilized to rapidly screen the potential ions of interest, while some functions of Peakview such as Formula Finder, XIC manager, and IDA Explorer were employed to facilitate the assignment or characterization of the screened astragalosides. A total of 42 astragalosides were screened and tentatively characterized or assigned, and 20 of them were firstly detected in Radix Astragali. According to the screened astragalosides, acetylation, glycosidation, hydrogenation, oxidation, and hydration were considered to be the major secondary metabolic pathways involved in the formation of the astragalosides. The combination of liquid chromatography with quadrupole time-of-flight mass spectrometry and automated Peakview analysis is a feasible and efficient tool to screen and identify the constituents in complex matrices of herbal medicines. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Hydroxysafflor yellow A (HSYA), the major active marker compound isolated from Carthamus tinctorius L. , has been demonstrated to possess various attractive pharmacological activities. However, there is a lack of information about the complete clinical pharmacokinetic profiles of HSYA following the administration of its pure preparations. The purpose of this study was to fully characterize the pharmacokinetic (PK) properties of HSYA in healthy Chinese volunteers following drip intravenous infusion of injectable powder of pure HSYA (IPPH), a new drug recently approved for the phase I clinical study by China Food and Drug Administration. Materials and methods 36 healthy subjects of either sex were recruited in this single-center, and open-label, single doses (25, 50, and 75 mg) and multiple doses (50 mg, once daily, 7 consecutive days) study. Plasma samples were analyzed with a validated LC–MS/MS method. Various PK parameters were estimated from the plasma concentration versus time data using non-compartmental methods. Results After single dose administration of IPPH, the values of AUC 0– t , AUC 0–∞ and C max for HSYA were statistically proportional over the dose range of 25–75 mg. After 7 repeated doses of 50 mg IPPH, both C max and AUC 0–∞ were significantly decreased, from 3207 to 2959 μg L −1 , and from 12,811 to 12,135 µg h L −1 respectively, while t 1/2 was significantly prolonged from 3.912 to 4.414 h. The minimum plasma concentrations on day 5, 6 and 7 showed good stability with no significant difference. Both C max and AUC of HSYA in male volunteers were generally lower than that in females. IPPH was generally well tolerated in healthy volunteers by either single or multiple dosing. Conclusion HSYA displayed moderately linear PK properties over the doses ranging from 25 to 75 mg of IPPH. Repeated administration of IPPH once daily could not lead to the in-vivo drug accumulation, but significantly affect PK behavior of HSYA. Gender difference should be considered for dosage recommendation in the clinic. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: Celastrol is a natural compound extracted from the traditional Chinese medicinal herb, Thunder God Vine (TGV). Owing to its potential anti-inflammatory and antitumor effects, celastrol has been considered as a promising candidate for drug development. Aim of the study: To establish a sensitive LC–MS/MS method to investigate the pharmacokinetic properties of celastrol in rats. Key pharmacokinetic issues of celastrol including oral bioavailability, comparative pharmacokinetics between pure compound and tablet preparation, as well as gender-related pharmacokinetic difference are to be addressed for the first time. Materials and methods: Sprague–Dawley rats were administrated an intravenous dose (100μgkg−1) of pure celastrol and an oral dose (1000μgkg−1) of pure celastrol and TGV tablets (corresponding to 534μgkg−1 of celastrol), respectively. At different time points, the concentration of celastrol in rat plasma was determined by a sensitive and well-validated LC–MS/MS method. Main pharmacokinetic parameters including area under the plasma concentration–time curve (AUC), maximal plasma concentration (Cmax), the time for maximal concentration (Tmax) and mean residence time (MRT) were estimated by Drug and Statistic1.0 pharmacokinetic software (Chinese Pharmacological Association, Anhui, PR China). Statistical analysis was performed using two one-side t test with p-values less than 0.05 as the level of significance. Results: The standard curve of celastrol showed good linearity in the concentration range of 0.11∼54.3ngmL−1 in our current method, with acceptable selectivity, precision, recovery, and stability. The oral absolute bioavailability of celastrol significantly increased from 17.06% for pure celastrol to 94.19% for TGV tablets containing equivalent celastrol. After oral administration of TGV tablets, the Cmax and AUC values of celastrol in female rats were (32.03±8.41)μgL−1 and (379.49±118.19)μghL−1, which were significantly higher (p<0.01) than that in males with the values of (14.31±7.33)μgL−1 and (188.17±92.33) μg hL−1. Conclusion: Celastrol administered orally in the rat was poorly absorbed into the systemic circulation. However, the poor absorption of celastrol could be greatly improved when celastrol-containing TGV tablets orally administered, and thereby the oral bioavailability of celastrol was significantly increased. As for gender difference, female rats showed significantly better absorption of celastrol than males. [Copyright &y& Elsevier]

Abstract: A rapid resolution liquid chromatography coupled with electrospray ionization (ESI) time-of-flight mass spectrometry method was developed and validated for quantitative analysis of 6-gingerol in plasma and various tissues. Liquid–liquid extraction was employed as sample preparation technique. Biological samples were separated on an Agilent Zorbax StableBond-C18 column (4.6mm×50mm, 1.8μm) and detected by TOF/MS with electrospray ionization (ESI) interface in positive ion mode. Calibration curves (1/x 2 weighted) offered satisfactory linearity (r 2 >0.995) within the test range. The lower limit of quantification in different matrices was in a range of 10–100ng/mL. Inter- and intra-day precision were in the range of 0.91–11.90% and 0.75–10.23%, respectively. Recoveries in plasma, urine and tissues ranged from 72.5% to 90.4%. Glucuronide of 6-gingerol, the major metabolite of 6-gingerol, was further determined after β-glucuronidase hydrolyzation. This developed method was successfully applied to pharmacokinetics, tissue distribution and excretion studies of 6-gingerol after oral or intraperitoneal administration in rats. [Copyright &y& Elsevier]

Abstract: In the present study, rapid resolution liquid chromatography was coupled with quadrupole time-of-flight tandem mass spectrometry (RRLC–Q-TOF–MS) to identify the absorbed components and metabolites in rat urine after oral administration of Buyang Huanwu decoction (BYHWD). After oral administration of BYHWD, urine samples were collected and pretreated by solid phase extraction. The mass measurements were accurate within 5ppm of error for all the protonated molecules, and subsequent fragment ions offered higher quality structural information for interpretation of the fragmentation pathways of various compounds. A total of 50 compounds were detected in rat urine samples within 20min, including 12 parent compounds and 38 metabolites. Except for three prototype components (Hydroxysafflor yellow A, Paeoniflorin, and Amygdalin), the metabolites identified mainly came from Radix Astragali, Radix Angelicae Sinensis, and Rhizoma Chuanxiong. The results indicated that glucuronidation and sulfation were the major metabolic pathways of isoflavonoids, while glutathione conjugation, glucuronidation and sulfation were the main metabolic pathways of phthalides. No saponin-related metabolites were detected. The present study provided important structural information on the metabolism of BYHWD. Furthermore, the results of this work have demonstrated the feasibility of the RRLC/ESI-Q-TOF–MS approach for rapid and reliable characterization of metabolites from herbal medicines. [Copyright &y& Elsevier]

Abstract: A sensitive and reliable high-performance liquid chromatography–mass spectrometry (HPLC–MS) was developed and validated for simultaneous quantification of five main bioactive components, i.e., calycosin-7-O-β-d-glucoside, ononin, astragaloside IV, astragaloside I and ferulic acid in rat plasma after oral administration of Danggui Buxue Tang (DBT) extract. Plasma samples were extracted with solid-phase extraction (SPE) separated on an Inertsil ZORBAX C18 column and detected by MS with electrospray ionization (ESI) interface in negative selective ion monitoring (SIM) mode. Calibration curves offered linear ranges of two orders of magnitude with r 2 >0.99. The method had the lower limit quantification of 0.55, 0.46, 1.07, 1.12 and 4.6ng/mL for calycosin-7-O-β-d-glucoside, ononin, astragaloside IV, astragaloside I and ferulic acid, respectively, with precision less than 10%. The RSD of intra- and inter-day variations ranged from 2.10% to 6.19% and 2.37% to 6.72%. This developed method was subsequently applied to pharmacokinetic studies of the five compounds in rats successfully. [Copyright &y& Elsevier]