High-throughput metabolomics discovers metabolite biomarkers and insights the protective mechanism of schisandrin B on myocardial injury rats.

Schisandrin B has been proved to possess anti-inflammatory and anti-endoplasmic effects, could improve cardiac function, inhibit apoptosis, and reduce inflammation after ischemic injury. However, the detailed metabolic mechanism and potential pathways of Schisandrin B effects on myocardial injury are unclear. Metabolomics could yield in-depth mechanistic insights and explore the potential therapeutic effect of natural products. In this study, the preparation of doxorubicin-induced myocardial injury rat model for evaluation of Schisandrin B on viral myocarditis sequelae related pathological changes and its mechanism. The metabolite profiling of myocardial injury rats was performed through ultra-high performance liquid chromatography combined with mass spectrometry combined with pattern recognition approaches and pathway analysis. A total of 15 metabolites (nine in positive ion mode and six in negative ion mode) were considered as potential biomarkers of myocardial injury, and these metabolites may correlate with the regulation of Schisandrin B treatment. A total of six metabolic pathways are closely related to Schisandrin B treatment, including glycerophospholipid metabolism, sphingolipid metabolism, purine metabolism, etc. This study revealed the potential biomarkers and metabolic network pathways of myocardial injury, and illuminated the protective mechanism of Schisandrin B on myocardial injury.

Prediction of lefamulin epithelial lining fluid penetration after intravenous and oral administration using Phase 1 data and population pharmacokinetics methods.

OBJECTIVES: Lefamulin is a semi-synthetic intravenous and oral pleuromutilin antibiotic with activity against pathogens commonly associated with community-acquired bacterial pneumonia. Using data from two Phase 1 studies, a population pharmacokinetics (PPK) model for lefamulin in plasma and epithelial lining fluid (ELF) was constructed. METHODS: Plasma pharmacokinetic (PK) data from a crossover, bioavailability, food-effect study and plasma and ELF PK data from a tissue penetration study in normal healthy volunteers were used to construct a PPK model for lefamulin. Model development involved refinement of a previous PPK model for intravenous and oral administration, followed by application of the model to plasma and ELF data from the tissue penetration study. The ELF penetration ratio of lefamulin was determined using model-based simulations. RESULTS: The PPK analysis data set contained 1103 plasma and 12 ELF lefamulin concentrations from 32 subjects. A three-compartment model with non-linear protein binding and two parallel absorption processes provided precise and unbiased estimated plasma concentration-time profiles. The absorption rate was slower and bioavailability was decreased after a high-fat/high-calorie meal. ELF data were well described using first-order rate constants into and out of the ELF compartment. The median predicted lefamulin total-drug ELF AUC0-24/free-drug plasma AUC0-24 ratio was ∼5:1 after intravenous or oral administration. CONCLUSIONS: The final PPK model allowed precise characterization of plasma and ELF exposures after intravenous and oral administration. The high ELF penetration ratio suggests that the penetration of lefamulin into the effect site is rapid and extensive, irrespective of route of administration.

Is the urban-adapted ring-billed gull a biovector for flame retardants?

Birds may act as biovectors of nutrients and contaminants at the regional scale and potentially increase the exposure to such substances in ecosystems frequented by these birds. However, no study has estimated biotransport of contaminants by individual birds through their feces (guano). Elevated concentrations of halogenated flame retardants (HFRs) have been reported in ring-billed gulls (Larus delawarensis) breeding near Montreal (QC, Canada)- a known hotspot for HFRs. The objective of the present study was to investigate the concentrations of polybrominated diphenyl ethers (PBDEs) and selected emerging HFRs (e.g., Dechlorane-related compounds) in guano of individual ring-billed gulls, and to assess the relative accumulation of these HFRs by comparing concentrations in plasma (absorbed) versus guano (excreted). A second objective was to determine the importance of one of the largest ring-billed gull colony (Deslauriers Island) in North America located near Montreal as a vector of HFR biotransport at the regional scale. Elevated concentrations of PBDEs and Dechlorane plus were determined in guano and plasma of ring-billed gulls, although in general no difference was found between males and females. However, plasma to guano concentration ratios were significantly greater in females for the highly hydrophobic BDE-209 and Dechlorane plus compared to males. Overall, for both sexes combined, the total amount of HFRs (sum of the 16 major PBDEs and five emerging HFRs) deposited by this entire colony (64,980 gulls) in the Montreal area through guano during the 28-days incubation period was estimated to 1 g. This study showed that urban-adapted ring-billed gulls from this large colony represent an underestimated biovector of HFRs, which may contribute to augment exposure to these toxic compounds in nearby ecosystems.

Simultaneous UPLC-MS/MS determination of four components of Socheongryong-tang tablet in human plasma: Application to pharmacokinetic study.

The purpose of this study was to develop a method for simultaneous analysis of schizandrin, ephedrine, paeoniflorin, and cinnamic acid as constituents of Socheongryong-tang tablet in human plasma using UPLC-MS/MS. These four components were separated using water containing 0.01% formic acid and methanol as a mobile phase by gradient elution at a flow rate of 0.3 mL/min with a HALO-C18 column (2.1 mm × 100 mm, 2.7 µm particle size). Quantitation was performed on a triple quadrupole mass spectrometer employing electrospray ionization technique operated in multiple reaction monitoring mode. Mass transitions were m/z 432.9 → 384.1 for schizandrin, 165.8 → 148.1 for ephedrine, 525.0 → 449.2 for paeoniflorin, 146.8 → 102.9 for cinnamic acid, and 340.0 → 324.0 for papaverine as internal standard. Liquid-liquid extraction and protein precipitation with ethyl acetate-methanol (1:2, v/v) were used to obtain these four components. Chromatograms showed high resolution, sensitivity, and selectivity without interference by plasma constituents. Calibration curves of schizandrin, ephedrine, paeoniflorin, and cinnamic acid in human plasma ranged from 0.02 to 8 ng/mL, 0.5 to 200 ng/mL, 0.2 to 80 ng/mL, and 1 to 400 ng/mL, respectively. Calibration curves of each analyte displayed excellent linearity, with correlation coefficients > 0.99. For all four components, both intra- and inter-day precisions (CV%) were <5.99%. The accuracy was 99.35-103.30% for schizandrin, 98.48-104.38% for ephedrine, 97.06-103.34% for paeoniflorin, and 99.97-104.36% for cinnamic acid. This analytical method developed in this study satisfied the criteria of international guidance. It could be successfully applied to pharmacokinetic studies of schizandrin, ephedrine, paeoniflorin, and cinnamic acid after oral administration of Socheongryong-tang tablet to humans.

Simultaneous quantification of Schisandrin B enantiomers in rat plasma by chiral LC-MS/MS: Application in a stereoselective pharmacokinetic study.

Schisandrin B (Sch B) has received much attention owing to its various biological activities. Schisandrin B exists as a racemate in "wuweizi", a traditional Chinese medicine in China. In the present study, a novel chiral LC-MS/MS method was developed for enantioselective separation and determination of Schisandrin B in rat plasma. The plasma samples were prepared by liquid-liquid extraction (LLE). Schisandrol B was used as internal standard. Chiral separation was obtained on a Chiralpak IC column using 0.1% (v/v) formic acid in mixture of methanol and water (90:10, v/v) as a mobile phase. Parameters including the selectivity, linearity, precision, accuracy, extraction recovery, matrix effect and stability were evaluated. The method described here is simple and reproducible. The lower limit of quantification of 5.0 ng/mL for each Sch B enantiomer permits the use of the method in investigating the stereoselective pharmacokinetics of Sch B. Following racemic Sch B and "wuweizi" extracts, the area under the curve of (8R, 8'S)-Sch B was statistically higher than the one of (8S, 8' R)-Sch B, with a ratio of 1.16-1.40 in three cases. This study firstly reports the development and validation of enantioselective behavior of Sch B in vivo, and provides a reference for clinical practice and encourages further research into Sch B enantioselective metabolism and drug interactions.

Brominated flame retardant (BFRs) and Dechlorane Plus (DP) in paired human serum and segmented hair.

Brominated flame retardants (BFRs) and Dechlorane Plus (DP) were measured in both human hair and paired serum samples from a cohort of university students in South China. Segmental analysis was conducted to explore gender difference and the relationships between the hair and serum. The concentrations of total PBDEs in the hair and serum samples were in a range of 0.28-34.1ng/g dry weight (dw) and 0.16-156ng/g lipid weight (lw), respectively. Concentrations of ∑DPs (sum of the syn-DP and anti-DP isomers) in all hair samples ranged from nd-5.45ng/g dry weight. Concentrations of most PBDEs and decabromodiphenylethane (DBDPE) in distal segments (5-10cm from the scalp) were higher than those in the proximal segments (0-5cm from the scalp) (t-test, p < 0.05), which could be due to the longer exposure time of distal segments. The proximal segments exhibited a unique congener profile, more close to that in the serum rather than the distal segments of hair. An obvious gender difference was found in the levels of ∑PBDEs using integrated hair samples, while the difference disappeared when considering alone the proximal segments of hair (0-5cm from scalp) for both genders. This paper provides supplement to the current knowledge on sources of BFRs and DPs in hair and declares the importance of segmental analysis.

Prediction of Drug-Drug Interaction between Tacrolimus and Principal Ingredients of Wuzhi Capsule in Chinese Healthy Volunteers Using Physiologically-Based Pharmacokinetic Modelling.

Schisantherin A and schisandrin A, the most abundant active ingredients of Wuzhi capsule, are known to inhibit tacrolimus metabolism by inhibiting CYP3A4/5. We aimed to predict the contribution of schisantherin A and schisandrin A to drug-drug interaction (DDI) between Wuzhi capsule and tacrolimus using physiologically-based pharmacokinetic (PBPK) modelling. Firstly, the inhibition mechanism of schisantherin A and schisandrin A on CYP3A4/5 was investigated. Thereafter, PBPK models of schisantherin A, schisandrin A and tacrolimus were established. Finally, tacrolimus pharmacokinetics were evaluated after the combined use with schisantherin A or schisandrin A. The blood area under the curve (AUC) of tacrolimus increased 1.77- and 2.61-fold after a single dose and multiple doses of schisantherin A, respectively. Meanwhile, schisandrin A inhibited tacrolimus metabolism to a smaller extent. Also, it showed that mechanism-based inhibition (MBI) played a more important role in DDI than reversible inhibition after long-term administration, while reversible inhibition was comparable to MBI after single-dose administration. In conclusion, we utilized PBPK modelling to quantify the contribution of schisantherin A and schisandrin A to DDI between tacrolimus and Wuzhi capsule. This may provide more insights for the rational use of this drug combination.

Development and validation of an LC-MS/MS method for the simultaneous quantification of seven constituents in rat plasma and application in a pharmacokinetic study of the Zaoren Anshen prescription.

A sensitive, specific and accurate liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the simultaneous determination of seven constituents of the Zaoren Anshen prescription (ZAP) in rat plasma after oral administration of the ZAP: spinosin, salvianic acid A, 6'''-feruloylspinosin, protocatechualdehyde, salvianolic acid B, schisandrin and deoxyschisandrin. The plasma samples and the internal standard (IS) sulfamethoxazole were extracted using acetonitrile. Chromatographic separation was performed with an Agilent HC-C18 column using a gradient elution profile and a mobile phase consisting of 0.01% formic acid in water (A) and acetonitrile (B). The analytes were quantified simultaneously in a single run using an ion trap mass spectrometer operated in the multiple reaction monitoring mode and electrospray ion-source polarity in the positive and negative modes. The calibration curves for spinosin, salvianic acid A, 6'''-feruloylspinosin, protocatechualdehyde, salvianolic acid B, schisandrin and deoxyschisandrin were linear over the concentration ranges of 2.90-1160, 2.50-1000, 1.80-720, 0.65-260, 2.50-1000, 8.00-1600 and 1.30-520 ng/mL, respectively. The intra- and inter-day precisions in terms of relative standard deviation were <18.9%, and the accuracies in terms of relative error were within ±14.2%. Consequently, the proposed method was successfully applied to the pharmacokinetic analysis of these seven major active compounds in rats administered ZAP. These results will facilitate research aiming to predict the effectiveness of the optimal dose of ZAP and might be beneficial for the therapeutic use of ZAP in the clinical setting.

Protective effects on myocardial infarction model: delivery of schisandrin B using matrix metalloproteinase-sensitive peptide-modified, PEGylated lipid nanoparticles.

PURPOSE: Schisandrin B (Sch B) is clinically applied for the treatment of hepatitis and ischemic disease. However, its clinical efficacy is limited due to the poor solubility and low bioavailability. This study aimed to develop matrix metalloproteinase (MMP)-sensitive peptide-modified, polyethylene glycol (PEG)-modified (PEGylated) solid lipid nanoparticles (SLNs) for loading Sch B (MMP-Sch B SLNs), and to evaluate the therapeutic effect in the myocardial infarction model. METHODS: PEG lipid and MMP-targeting peptide conjugate were synthesized. MMP-Sch B SLNs were prepared by solvent displacement technique. The physicochemical properties and pharmacokinetics of SLNs were investigated. In vivo effects on infarct size was evaluated in rats. RESULTS: The successful synthesis of lipid-peptide conjugate was confirmed. MMP-Sch B SLNs had a particle size of 130 nm, a zeta potential of 18.3 mV, and a sustained-release behavior. Higher heart drug concentration and longer blood circulation times were achieved by Sch B loaded SLNs than the drug solution according to the pharmacokinetic and biodistribution results. The best therapeutic efficacy was exhibited by MMP-Sch B SLNs by reducing the infarction size to the greatest extent. CONCLUSION: The modified SLNs may be a good choice for delivery of Sch B for the treatment of myocardial infarction.

A sensitive UHPLC-MS/MS method for the simultaneous quantification of three lignans in human plasma and its application to a pharmacokinetic study.

The aim of this study was to develop an analytical method to simultaneously analyze schizandrin, schizandrol B, and gomisin N lignans in human plasma using ultra high performance liquid chromatography with tandem mass spectrometry. The three lignans were separated using a mobile phase of water and acetonitrile containing 0.02% acetic acid equipped with a Kinetex C18 column (2.1 mm × 50 mm, 1.7 µm). This analysis was achieved by multiple reaction monitoring mode in an electrospray interface. The mass transitions were m/z 433.1→384.0 for schizandrin, 398.8→367.8 for schizandrol B, and 400.6→299.8 for gomisin N. Liquid-liquid extraction with methyl tert-butyl ether was used to obtain the three lignans. The chromatograms showed high resolution, sensitivity, and selectivity with no interference with plasma constituents. The calibration curves for the three lignans in human plasma were 0.05-50 ng/mL and displayed excellent linearity with correlation coefficients greater than 0.99. Precision for all three lignans was within 11.23%. The accuracy was 88.3-99.0% for schizandrin, 90.6-103.4% for schizandrol B, and 90.2-103.5% for gomisin N. The developed simultaneous analytical method satisfied the criteria of international guidance and could be successfully applied to the pharmacokinetic study of three lignans after oral administration of Schisandrae Fructus extract powder to humans.

Current halogenated flame retardant concentrations in serum from residents of Shandong Province, China, and temporal changes in the concentrations.

The residents of Shandong Province, China, are exposed to high concentrations of halogenated flame retardants because large amounts of halogenated flame retardants are produced in the province. We determined the concentrations of eight polybrominated diphenyl ether congeners (PBDEs), seven novel brominated flame retardants (NBFRs), and the two dechlorane plus isomers (DPs) in serum from residents of Shandong Province. The aim was to identify temporal trends in the concentrations of these pollutants. The mean total concentrations of PBDEs, NBFRs and DPs were 41, 2.2 and 2.1ng/g lipid in pooled serum samples collected in 2014, and were 32, 3.5 and 3.1ng/g lipid in pooled serum samples collected in 2015, respectively. Decabromodiphenyl ether was the dominant PBDE congener in all of the samples. The novel brominated flame retardant and dechlorane plus concentrations were between one and two orders of magnitude lower than the PBDE concentrations. The PBDE concentrations in serum decreased significantly between 2007 and 2015, but the pentabromobenzene, pentabromotoluene, and dechlorane plus concentrations were relatively stable.

Simultaneous determination of wogonin, oroxylin a, schisandrin, paeoniflorin and emodin in rat serum by HPLC-MS/MS and application to pharmacokinetic studies.

Wogonin and oroxylin A in Scutellariae Radix, schisandrin in Chinensis Fructus, paeoniflorin in Moutan Cortex and emodin in Polygoni Cuspidate Rhizome et Radix are anti-inflammatory active compounds. A method for simultaneous determination of the five compounds in rat was developed and validated using high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS). The separation was performed on a Symmetry C18 column (4.6 × 50 mm, 3.5 µm) with acetonitrile and 0.1% formic acid aqueous solution as the mobile phases. The detection was performed using multiple-reaction monitoring with electrospray ionization source in positive-negative ion mode. The calibration curves showed good linearity (r ≥ 0.9955). The lower limit of quantification (LLOQ) was 5 ng/mL for wogonin and schisandrin, 10 ng/mL for oroxylin A and emodin, and 15 ng/mL for paeoniflorin, respectively. The relative standard deviations of intraday and interday precisions were <11.49 and 14.28%, respectively. The extraction recoveries and matrix effects were acceptable. The analytes were stable under the experiment conditions. The validated method has been successfully applied to pharmacokinetic studies of the five compounds in rats after oral administration of Hu-gan-kan-kang-yuan capsule. This paper would be a valuable reference for pharmacokinetic studies of Chinese medicine preparations containing the five compounds.

Occurrence of Dechlorane compounds and polybrominated diphenyl ethers (PBDEs) in the Korean general population.

Dechlorane compounds, including Dechlorane Plus (DP), mirex, and Dechlorane (Dec) 602, 603 and 604, were measured in 61 serum samples collected from a Korean urban area (Seoul) in 2013. Dechlorane Plus and Dec 602 were dominant in most samples, whereas Dec 604 was not detected in any samples. The median value of DP was 0.75 ng/g lipid, which was comparable with the levels observed in Europe and Canada, but lower than that observed in China. Statistically significant correlations among Dechlorane compounds were observed. The median anti-isomer fractional abundance (fanti) was 0.74, and a negative correlation between fanti and the DP concentration in serum samples was observed. Polybrominated diphenyl ethers (PBDEs) were also measured for comparison with Dechlorane compounds, and BDE-153 was found the most abundant congener with a median value of 1.43 ng/g lipid. A time trend of Dechlorane compounds was investigated in 7 pooled serum samples to cover the period from 2006 to 2013. A distinct trend of Dechlorane compounds was not observed, while PBDEs steadily decreased with time.

Maternal transfer of dechloranes and their distribution among tissues in contaminated ducks.

The tissue concentrations of dechlorane plus and its analogues were determined in ducks collected from several e-waste recycling villages of Taizhou, China. Compared with the published literature, the relatively high concentrations of these compounds were detected in ducks, indicating serious DP contamination. Since both the duck meat and eggs were important components for diet, this result reminded us of keeping a watchful eye on human dietary exposure to DP and its analogues in this study area. The wet-weight concentrations of DP and its analogues were significantly related to tissue lipid content (p < 0.05), indicating that the lipid pools predominantly impacted the distribution of DPs in ducks. On the basis of lipid adjustment, the significantly lower levels in brain than those in liver and blood, displayed the occurrence of liver sequestration and blood-brain barrier to DP and its analogues in the duck (p < 0.05). The maternal transfer of DP and Mirex was not obviously limited, and the transferring extent of Dec 602 was over one. The stereo-selected accumulation of two DP isomers occurred among tissues with preference to syn-DP in blood, and to anti-DP in brain. The values of lipid-adjusted monodechlorinated products mainly originated from the exterior environment in ducks.

Comparing human exposure to emerging and legacy flame retardants from the indoor environment and diet with concentrations measured in serum.

This study investigates associations between serum concentrations of emerging and legacy halogenated flame retardants (HFRs) in 46 Norwegian women and measured indoor air and dust concentrations of the HFRs as well as detailed information on diet and household factors. Hexabromobenzene (median 0.03ng/g lipid) and Dechlorane 602 (median 0.18ng/g lipid) were detected in about 50% of the samples and Dechlorane Plus syn (median 0.45ng/g lipid) and anti (median 0.85ng/g lipid) in more than 78%. The most abundant polybrominated diphenyl ethers were 2,2',4,4',5,5'-hexabromodiphenyl ether (BDE-153; median 0.82ng/g lipid) and 2,2',4,4'-tetrabromodiphenyl ether (BDE-47; median 0.49ng/g lipid) detected in more than 70% of the samples. In the bivariate analysis, no consistent associations were observed between the biomonitoring data and measured concentrations in indoor air and dust. On the other hand, consumption of specific food items (mainly lamb/mutton and margarine) correlated significantly with more than two HFR serum concentrations, while this was not the case for household factors (electronic appliances). Only the significant bivariate associations with diet were confirmed by multivariate linear regression analyses, which might indicate a higher contribution from food compared to the indoor environment to the variation of the body burden of these HFRs.

Dechlorane Plus in paired hair and serum samples from e-waste workers: correlation and differences.

Dechlorane Plus (DP) and a dechlorinated product of DP were measured in 34 matched human hair and serum samples (19 males and 15 females) collected from e-waste recycling workers in South China. The DP (sum of syn- and anti-DP) concentrations in hair and serum samples ranged from 6.3 to 1100 ng g(-1) dry weight and from 22 to 1400 ng g(-1) lipid weight (lw). The levels of anti-Cl11-DP ranged from 0.02 to 1.8 ng g(-1) in hair and from not detected to 7.9 ng g(-1) lw in serum. Significant positive correlations for both DP and anti-Cl11-DP concentrations between hair and serum samples were found (p<0.05), indicating hair to be a suitable matrix for human DP exposure. However, a significant difference was found in the DP isomer composition between hair and serum, suggesting stereoselective bioaccumulation during the absorption of DP into hair. A sharp gender difference was found in the levels of DP in hair. Moreover, syn-DP, anti-DP and anti-Cl11-DP in hair significantly correlated with those in serum for male samples, but not for female samples. The observed gender differences in the present study may be, in part, ascribed to the much longer hair exposure time for females than males due to the difference in sampling distance from the scalp.

Time and dose relationships between schisandrin B- and schisandrae fructus oil-induced hepatotoxicity and the associated elevations in hepatic and serum triglyceride levels in mice.

BACKGROUND: Schisandrin B (Sch B), a dibenzocyclooctadiene compound, is isolated from schisandrae fructus (SF). This study was conducted to compare the time- and dose-response between Sch B- and SF oil (SFO)-induced changes in hepatic and serum parameters in mice. METHODS: Institute of Cancer Research (ICR) mice were given a single oral dose of Sch B (0.125-2 g/kg) or SFO (0.3-5 g/kg). Serum alanine aminotransferase (ALT) activity, hepatic malondialdehyde, and triglyceride (TG) levels were measured at increasing time intervals within 6-120 hours postdosing. RESULTS: Serum ALT activity was elevated by 60%, with maximum effect (E(max)) = 45.77 U/L and affinity (K(D)) = 1.25 g/kg at 48-96 hours following Sch B, but not SFO, treatment. Sch B and SFO treatments increased hepatic malondialdehyde level by 70% (E(max) =2.30 nmol/mg protein and K(D) =0.41 g/kg) and 22% (E(max) = 1.42 nmol/mg protein and K D = 2.56 g/kg) at 72 hours postdosing, respectively. Hepatic index was increased by 16%-60% (E max = 11.01, K(D) = 0.68 g/kg) and 8%-32% (E(max) = 9.88, K D = 4.47 g/kg) at 12-120 hours and 24-120 hours after the administration of Sch B and SFO, respectively. Hepatic TG level was increased by 40%-158% and 35%-85%, respectively, at 12-96 hours and 6-48 hours after Sch B and SFO treatment, respectively. The values of E max and K D for Sch B/SFO-induced increase in hepatic TG were estimated to be 22.94/15.02 µmol/g and 0.78/3.03 g/kg, respectively. Both Sch B and SFO increased serum TG (up to 427% and 123%, respectively), with the values of E(max) = 5.50/4.60 mmol/L and K D = 0.43/2.84 g/kg, respectively. CONCLUSION: The findings indicated that Sch B/SFO-induced increases in serum/hepatic parameters occurred in a time-dependent manner, with the time of onset being serum TG level < hepatic TG level < hepatic index < serum ALT activity. However, the time of recovery of these parameters to normal values varied as follow: serum TG level < hepatic TG level and liver injury < hepatic index. The E max and affinity of Sch B on tissue/enzyme/receptor were larger than those of SFO.

Simultaneous determination of calycosin-7-O-ß-d-glucoside, calycosin, formononetin, astragaloside IV and schisandrin in rat plasma by LC-MS/MS: application to a pharmacokinetic study after oral administration of Shenqi Wuwei chewable tablets.

A rapid, sensitive and reliable high-performance liquid chromatography-mass spectrometry (LC-MS/MS) method was developed and validated for simultaneous quantification of the five main bioactive components, calycosin, calycosin-7-O-ß-d-glucoside, formononetin, astragaloside IV and schisandrin in rat plasma after oral administration of Shenqi Wuwei chewable tablets. Plasma samples were extracted using solid-phase extraction separated on a CEC18 column and detected by MS with an electrospray ionization interface in multiple-reaction monitoring mode. Calibration curves offered linear ranges of two orders of magnitude with r > 0.995. The method had a lower limit of quantitation of 0.1, 0.02, 0.1, 1 and 0.1 ng/mL for calycosin, calycosin-7-O-ß-d-glucoside, formononetin, astragaloside IV and schisandrin, respectively. Intra- and inter-day precisions (relative standard deviation) for all analytes ranged from 0.97 to 7.63% and from 3.45 to 10.89%, respectively. This method was successfully applied to the pharmacokinetic study of the five compounds in rats after oral administration of Shenqi Wuwei chewable tablets.

Comparative pharmacokinetics and tissue distribution of schisandrin, deoxyschisandrin and schisandrin B in rats after combining acupuncture and herb medicine (schisandra chinensis).

Recently, combination therapy with acupuncture and medicine as a practical strategy to treat diseases has gained increasing attention. The present study aimed to investigate whether acupuncture stimulation at ST.36 had a potential impact on the pharmacokinetics and tissue distribution of lignans. An HPLC-ESI/MS analytical method was established and successfully applied to a comparative study of drug concentration in plasma and tissues of three lignans. The parameters area under the plasma concentration-time curve from time zero to the final measurable point and from time zero to infinity, and peak concentration were significantly increased, with a prolonged mean residence time and a corresponding decrease in clearance in comparision with the Schisandra-alone group. Additionally, tissue concentrations of three lignans were improved in the group with acupuncture, especially in liver. The results indicated that acupuncture has a synergistic effect on the pharmacokinetics and tissue distribution of the three lignans, which could postpone their elimination, resulting in a longer blood circulating time in rat plasma and prolonged residence time in target tissues, leading to higher tissue concentration. The findings provide some scientific evidence for the mechanism of the combined use of acupuncture and herbal medicine. Furthermore, we suggest that acupuncture and its combination with herbal medicine should be investigated further as a possible adjuvant therapy in clinical treatment for liver injury.

Assessment on the occupational exposure of manufacturing workers to Dechlorane Plus through blood and hair analysis.

Dechlorane Plus (DP), as a widely used flame retardant in different electrical and textile applications, has recently attracted great concern around the world. The present study investigated the DP levels and distribution in human samples from a DP manufacturing plant and a nearby area in east China. The DP concentrations ranged from 89.8 to 2958 ng/g lipid weight in whole blood and 4.08 to 2159 ng/g dry weight in hair. For the workers engaged in DP manufacturing process, their DP levels were significantly higher than those in most of the other two control groups from the nearby area. The values of anti-DP fractional abundance (fanti ratio) were commonly lower in the human samples from both the manufacturing plant and nearby area compared with those in the commercial products, and excretion as well as biotransformation are possible reasons for stereoselective accumulation of the syn-DP isomer in humans. Furthermore, a significantly positive relationship (p < 0.05) was obtained between (i) the concentrations (and fanti) in the paired blood and hair samples, indicating a similar distribution pattern of the two DP isomers in the paired samples; (ii) the DP levels in human body and the exposure time (p < 0.05), which suggests that further assessment could be needed to investigate potential long-term risks to the occupational population.