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Ethnopharmacological relevance Pharmacokinetic studies on traditional Chinese medicine are useful to evaluate and predict the drug efficacy and safety. The renal impairment may affect drug clearance and other pharmacokinetic processes which can increase toxicity and drug to drug interactions or cause ineffective therapy. Pharmacokinetic studies in pathological status rats might be meaningful for revealing the action mechanism and improving clinical medication of the herb medicine. Materials and methods A highly sensitive and rapid ultra-performance liquid chromatography–mass spectrometry (UPLC–MS) method with multiple-reaction monitoring (MRM) mode was developed and validated for simultaneous quantitation of morroniside and loganin in normal and doxorubicin-induced chronic kidney disease (CKD) rat plasma after oral administration of Shanzhuyu (fruit of Cornus officinalis ) extract. Results Both calibration curves gave satisfactory linearity ( r >0.99) at linear range of 1.96–1962.5 ng mL −1 for morroniside, 1.53–1531.25 ng mL −1 for loganin. The precision and accuracy of the in vivo study were assessed by intra-day and inter-day assays. The percentages of relative standard deviation (RSD) were all within 9.58% and the accuracy (RE) was in the −6.02% to 8.11% range. The extraction recoveries of morroniside, loganin and internal standard (IS) were all >67.62% and the matrix effects ranged from 95.07% to 102.75%. Conclusions The pharmacokinetic behavior of morroniside and loganin in normal and CKD rat plasma was determined in this paper. The significant different pharmacokinetic parameters might partly result from the changes of P-glycoprotein and metabolic enzymes in the pathological state. The pharmacokinetic research in the pathological state might provide more useful information to guide the clinical usage of the herb medicine. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: The dried fruit of Psoralea corylifolia L. has been used to prevent and treat vitiligo, osteoporosis, arthralgia and asthma in Traditional Chinese Medicine for some 1600 years. Psoralen (P), isopsoralen (IP), psoralenoside (PO) and isopsoralenoside (IPO) are the major coumarins and coumarin-related benzofuran glycosides in Psoraleae Fructus, which have been reported to show estrogen-like activity, osteoblastic proliferation accelerating activity, antitumor effects and antibacterial activity. The first aim of this study is to develop a rapid, sensitive and selective ultra performance liquid chromatography tandem mass spectrometry (UPLC–MS/MS) approach for simultaneous determination of PO, IPO, P and IP in rat plasma and samples collected from in vitro incubation experiments. The second aim is to investigate the pharmacokinetic properties of PO, IPO, P and IP after oral administration of Psoralea corylifolia extract (PCE) to rats. The third aim is to confirm the biotransformation of PO to P or IPO to IP under gastrointestinal conditions. Materials and methods: A UPLC–MS/MS method with a C18 column and a mobile phase of methanol-0.1% aqueous formic acid was validated according to the criteria in FDA guidelines about bioanalytical method, which was developed to investigate the pharmacokinetic behavior of PO, IPO, P and IP from PCE and the metabolic pathways of PO to P or IPO to IP. Results: The criteria for establishment of a new UPLC–MS/MS method including selectivity, linearity, accuracy, precision, extraction recovery, matrix effect and stability were validated. This method was successfully applied to the quantitative determination of PO, IPO, P and IP in biological samples collected from both in vitro incubations and in vivo rat experiments. After oral administration of PCE to rat, pharmacokinetic parameters of these four compounds indicated that in vivo biotransformation may occur between PO and P or IPO and IP. Purified benzofuran glycosides fraction (PBGF), containing only PO and IPO, was orally administered to rats to further confirm the biotransformation of PO to P or IPO to IP under gastrointestinal conditions. An in vitro incubation study elucidated that PO and IPO were metabolized to P and IP by intestinal microflora through de-glucosylation. Conclusions: This paper developed a rapid, sensitive and selective UPLC–MS/MS method for simultaneous determination of PO, IPO, P and IP from PCE in biological samples, and investigated on their comprehensive in vivo and in vitro pharmacokinetic studies. These obtained results showed that the metabolism by intestinal bacteria plays an important role in pharmacological effects of orally administered PCE. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: Acanthopanax sessiliflorus (Rupr. et Maxim.) Seem. is a shrub mainly present in China, Japan and Korea, the root bark of which is considered as one of the sources of Wujiapi and widely used for its various pharmacological effects. Aim of the study: A selective and sensitive UPLC–MS/MS method was developed and validated for the determination and pharmacokinetic study of asarinin, sesamin, helioxanthin and savinin in rat plasma. Materials and methods: Sample preparation involved a liquid–liquid extraction of the analytes with methyl tert-butyl ether (MTBE). LC separation was achieved on a UPLC C18 column at 30°C with a mobile phase consisting of methanol–2mM ammonium acetate (68:32, v/v). The detection was accomplished by multiple-reaction monitoring (MRM) scanning with electrospray ionization (ESI) source operating in the positive ionization mode. The optimized mass transition ion-pairs (m/z) monitored for asarinin, sesamin, helioxanthin, savinin and IS were 372.2/233.0, 372.2/233.0, 349.1/319.0, 352.9/334.9 and 180.0/109.7, respectively. Results: The current LC–MS/MS assay was validated for linearity, intra-day and inter-day precisions, accuracy, extraction recovery and stability and was suitable for pharmacokinetic studies of the four lignans after oral administration of Acanthopanax sessiliflorus extract. The time to reach the maximum plasma concentration (T max) was 2.50±0.15h for asarinin, 1.94±0.28 for sesamin, 2.22±0.48h for helioxanthin and 2.83±0.29h for savinin. The elimination half-time (t 1/2) of asarinin, sesamin, helioxanthin and savinin was 6.08±1.10, 11.69±0.50, 7.16±0.52 and 6.26±0.57h, respectively. Conclusion: This paper described a simple, sensitive and validated UPLC–MS/MS method for simultaneous determination of four lignans in rat plasma after oral administration of Acanthopanax sessiliflorus extract, and investigated on their pharmacokinetic studies as well. [Copyright &y& Elsevier]

Abstract: Ethnopharmacological relevance: Traditional Chinese medicine (TCM) has been used in clinical practice for several thousand years. TCM has played an indispensable role in the prevention and treatment of diseases, especially the complicated and chronic ones. Pharmacokinetic study on active constituents in herbal preparations is a good way for us to explain and predict a variety of events related to the efficacy and toxicity of TCM. Aim of the study: A selective and sensitive HPLC–MS/MS method was first developed and validated for the determination of luteolin, kaempferol, apigenin, quercetol, and isorhamnetin in rat plasma. Materials and methods: The LC system consisted of an Agilent Technologies Series 1200 system (Agilent, USA) equipped with an automatic degasser, a quaternary pump, and an autosampler. Chromatographic separations were performed on a Waters SunFire™ C18 column (150mm×4.6mm, 5μm), and the column temperature was maintained at 25°C and the sample injection volume was 20μL. The current LC–MS/MS assay was validated for linearity, intra-day and inter-day precisions, accuracy, extraction recovery and stability. Results: The validated method was successfully applied to monitoring the concentrations and pharmacokinetic studies of five flavone compounds in rat plasma after a single oral administration of Verbena officinalis L. extract with a dosage of 8.0mL/kg. The time to reach the maximum plasma concentration (T max1) was 0.48±2.14h for luteolin, 0.25±0.13h for kaempferol, 0.97±1.08h for apigenin, 1.04±4.25h for quercetol and 0.25±0.16h for isorhamnetin, and the maximum plasma concentration (T max2) was 3.97±1.48h, 4.05±0.46h, 4.33±0.58h, 2.99±0.48h and 4.02±0.34h. The elimination half-time (t 1/2) of luteolin, kaempferol, apigenin, quercetol and isorhamnetin was 4.02±0.81, 7.65±0.71, 3.30±0.83, 4.55±0.49 and 5.56±1.32h, respectively. Conclusions: This paper described a simple, sensitive and validated LC–MS/MS method for simultaneous determination of luteolin, kaempferol, apigenin, quercetol and isorhamnetin in rat plasma after oral administration of V. officinalis L. extract, and investigated on their pharmacokinetic studies as well, with a short run time of 5min. [Copyright &y& Elsevier]

Abstract: In this paper, microdialysis combined with ultra performance liquid chromatography/mass spectrometry (UPLC-MS) was applied for the determination of ligustilide in freely moving rats'' brain. The extracellular unbound ligustilide could be detected in rat brain within the first time interval (0–20min) after nasal administration but not after oral administration. This result showed that ligustilide could quickly enter the brain after nasal administration; which implied that ligustilide may have a rapid onset of action. This work demonstrated the potential application of microdialysis combined with UPLC-MS in pharmacokinetic studies. Furthermore, the advantage that fewer animals used in the microdialysis experiment was confirmed. [Copyright &y& Elsevier]