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Bi qi capsule (BQC) is a traditional Chinese medicine prescription that is clinically used for the treatment of rheumatoid arthritis. Strychnine and brucine, as two typical kinds of alkaloids, are the primary active and neurotoxic constituents of BQC. In this study, a sensitive and reliable rapid resolution liquid chromatography-tandem mass spectrometry (RRLC-MS/MS) quantitative method was used to determine the concentrations of brucine and strychnine in rat brain and blood dialysates. The blood-brain barrier (BBB) penetration of free brucine and strychnine and their pharmacokinetic characteristics were investigated by the validated RRLC-MS/MS method coupled with in vivo microdialysis for the first time. The dialysate brain-blood AUC ratios of brucine were 0.098, 0.44 and 0.40 respectively at 0.4, 0.8 and 1.6 g kg −1 doses of BQC, and the dialysate brain-blood AUC ratios of strychnine were 0.20, 1.25 and 2.06 respectively at 0.4, 0.8 and 1.6 g kg −1 doses of BQC. The high brain-blood AUC ratios of brucine and strychnine were observed in medium and high dose groups of BQC. In addition, the effects of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) on brucine and strychnine across BBB were also studied using the above method as well as molecular docking. The results prompted that brucine was the substrate of P-gp, and strychnine might be the inhibitor of P-gp. Brucine and strychnine showed high brain penetration, so it is very important to well control the clinic dosage of BQC and manufactory quality for avoiding the side effects and obtaining good therapeutic efficacy. Our study could be further used in investigating BBB penetration for other drugs caused neurotoxicity. [ABSTRACT FROM AUTHOR]

A sensitive and high-efficiency method for simultaneous detection of pyraclostrobin, prochloraz, and its metabolite in apple and soil based on QuEChERS pretreatment combined with rapid resolution liquid chromatography tandem mass spectrometry was established and validated. The limits of quantification of three compounds in two matrixes were 0.005 mg kg−1. The average recoveries of pyraclostrobin, prochloraz, and 2,4,6-trichlorophenol in soil matrix were in the ranges of 87-105%, 86-95%, and 90-96%, respectively, with all the relative standard deviations (RSDs) of < 9.6%, while recoveries were 89-93%, 83-97%, and 89-101% in apple with the RSDs of < 6.5% at three spiking levels. For verify the applicability of this method, the real samples from three representative locations were detected. The degradation behaviors and residue distributions of pyraclostrobin and prochloraz and its metabolite in apple ecosystem were investigated. The field experiment data showed that the dissipation of pyraclostrobin and prochloraz in apple and soil followed pseudo-first-order kinetic models. The half-lives of pyraclostrobin in soil and apple were 8.6-19.8 and 7.9-15.1 days, while prochloraz were 8.9-21 and 5.8-12.4 days. The highest terminal residue of total prochloraz and pyraclostrobin in apple, after spraying three to four times with the interval of 28 days, was far below the maximum residue limits recommended by China. This research could provide guidance on a reasonable usage of prochloraz and pyraclostrobin in apple orchard. [ABSTRACT FROM AUTHOR]

Abstract: Biqi capsule is a well‐known traditional Chinese medicine formula that has been widely applied for the clinical treatment of such diseases as rheumatoid arthritis, scapulohumeral periarthritis and cervical spondylopathy. However, there is concern regarding the toxicity of Biqi capsule owing to its active ingredients, strychnine and brucine. To investigate the toxicokinetics of strychnine and brucine after oral administration of Biqi capsule to rats, a sensitive and simple rapid‐resolution liquid chromatography/tandem mass spectrometry method was developed to determine the levels of strychnine and brucine in rat plasma. Chromatographic separation was performed on a Capcell Pak C18 MG II (3.0 μm, 2.0 × 35 mm) column by gradient elution with acetonitrile and 0.2% formic acid as the mobile phase. The method was validated over the range of 0.25–250 ng/mL for strychnine and 0.025–25 ng/mL for brucine. The intra‐ and inter‐day accuracies of strychnine and brucine in rat plasma were 100.3–106.6 and 90.75–106.1% respectively, and the precisions were within 14.2%. The established method was successfully applied to the toxicokinetic study of strychnine and brucine after single and multiple oral administration of Biqi capsule to male and female rats at 0.4, 0.8 and 1.6 g/kg doses. The results showed different toxicokinetic characteristics in the different groups. [ABSTRACT FROM AUTHOR]

Naftopidil (NAF) is used as a racemate to treat benign prostatic hyperplasia (BPH) and to prevent prostate cancer. However, racemic NAF has low bioavailability; therefore, it is commonly administered at higher clinical dosages compared to other therapeutic BPH drugs. Differences in interactions between individual enantiomers and biological macromolecules may result in variations in pharmacokinetics and dispositions. This study aimed to investigate the pharmacokinetics, bioavailability and tissue distributions of NAF enantiomers in rats after intragastric administration of the individual enantiomers. A rapid and sensitive liquid chromatography coupled with triple–quadrupole mass spectrometric method (RRLC–MS/MS) was developed and validated for determination of NAF enantiomers in rat plasma, tissues, urine and feces. After intragastric administration, S (−)-NAF in plasma [maximum concentration ( C max ) = 186.4 ng/mL, area under the curve from 0 h to 24 h (AUC 0–24 h ) = 877.9 ng h/mL] was significantly higher than that of R (+)-NAF ( C max = 133.2 ng/mL, AUC 0–24 h = 602.1 ng h/mL). Moreover, S (−)-NAF bioavailability was twice that of R (+)-NAF. R (+)-NAF distributions in the prostate, liver, and kidney were significantly higher than S (−)-NAF distributions ( R / S ratios of 3.16, 1.33, and 2.90, respectively). These data reveal the stereoselective pharmacokinetic profiles of the two enantiomers in rats. [ABSTRACT FROM AUTHOR]

Background Shen-Fu decoction is a traditional Chinese medicine prescription with a 3:2 ratio of Radix Ginseng and Fuzi (Radix Aconiti lateralis praeparata). Ginsenosides and alkaloids are considered to be the main active components of Shen-Fu decoction. However, no analytical methods have been used to quantitatively analyse both components in Shen-Fu decoction simultaneously. Results We successfully developed a rapid resolution liquid chromatography coupled with tandem mass spectrometry (RRLC-MS/MS) method for the simultaneous analysis of seven ginsenosides and three aconitum alkaloids in Shen-Fu decoction, the decoction of Radix ginseng and Fuzi (Radix Aconiti lateralis praeparata). Chromatogrpahic separation by RPLC was achieved using a reversed-phase column and a water/acetonitrile mobile phase, containing 0.05% formic acid and using a gradient system. The method was optimized to allow for simultaneous analysis of all analytes in 11minutes without the need for baseline resolution of the components. Furthermore, the separation demonstrated good linearity (r > 0.9882), repeatability (RSD < 7.01%), intra- and inter-day precisions (RSD < 5.06%) and high yields of recovery (91.13-111.97%) for ten major constituents, namely ginsenoside-Re, Rg1, Rb1, Rc, Rb2, Rd, Rf, aconitine, hypacoitine and mesaconitine. Conclusions The developed method could be used as a rapid and reliable approach for assessment of the quantity of the major constituents in Shen-Fu decoction. [ABSTRACT FROM AUTHOR]

Abstract: A novel multiresidue analysis method is developed for highly sensitive and simultaneous determination of 16 sulphonamides (SAs), 4 acetyled metabolites, and trimethoprim in pork and mutton by rapid resolution liquid chromatography-tandem mass spectrometry (RRLC-MS/MS). The sample was extracted with acetonitrile under ultrasonication incubation, followed by solid phase extraction (SPE). The calibration curves showed good linearity with correlation coefficient (r) more than 0.998. The limit of quantification (LOQ) was 0.35–1.0 μg/kg, which can ensure to detect studied drugs at the maximum residue level (MRL) of 10 μg/kg. The mean recoveries at addition level of 1.0, 5.0 and 50 μg/kg were in the range of 68.3–104% with the relative standard deviation (RSD) of 3.5–9.2%. The intra-day precision (as RSD) for six determinations at 50 μg/kg spiked level within a day was in the range of 4.2–8.9%. The method is sensitive, accurate, convenient and rapid, and can be used for the qualitatively and quantitatively determination of multiresidue of the studied drugs in meat. [Copyright &y& Elsevier]

Abstract: The identification and quantification of saponins in crude extracts are challenging because of their similar structures and weak ultraviolet absorption. In this study, a rapid resolution liquid chromatography coupled with triple quadruple electrospray tandem mass spectrometric method was established to identify and quantify steroid saponins in the rhizomes of Dioscorea panthaica Prain et Burk, a traditional Chinese medicine. Six steroid saponins were simultaneously determined and quantified within 9min. All analytes were subjected to a RP-18e (50mm×2mm) monolithic column using a gradient elution program with a final detection using electrospray ionization tandem mass spectrometry in the negative ionization mode. The rapid resolution liquid chromatography/tandem mass spectrometry method achieved a limit of detection ranging from 0.52 to 20.40ngmL−1 and a limit of quantification ranging from 1.20 to 75.20ngmL−1 for the six studied steroidal saponins. The intra-day and inter-day precision (RSD) were less than 5.34%, and the recovery (RSD) was 1.50–3.51%. The highly sensitive and rapid method is suitable for the quantification of steroidal saponins in D. panthaica rhizomes. [Copyright &y& Elsevier]

Abstract: A robust and sensitive analytical method is presented in which 11 classes of antibiotics are simultaneously extracted and determined in surface water, lagoon wastewater, influent, effluent, sediment, manure and sludge. Water samples with different volumes were adjusted to pH 3, added with 0.2g Na2EDTA and then extracted using Oasis hydrophilic–lipophilic balance (HLB) cartridges. Extraction of solid samples was carried out by a combination of ultrasonic and vortex mixing using a mixture of acetonitrile and citric buffer at pH 3 as the extraction solution. The extracts of the solid samples were then cleaned-up by a tandem solid phase extraction (SPE) method using a strong anion exchange cartridge (SAX) and a HLB cartridge, followed by analysis using rapid resolution liquid chromatography–tandem mass spectrometry (RRLC–MS/MS) equipped with electrospray ionization source. Among the 50 target compounds, the recoveries in the range of 50–150% were obtained for 39, 40, 36, 40, 38, 33 and 36 antibiotics in the spiked samples of surface water, lagoon wastewater, influent, effluent, sediment, manure and sludge with three concentrations, respectively. Method quantification limits (MQLs) for the target compounds (except sulfaguanidine and sulfanilamide) were in the range of 0.52–5.88ng/L, 2.36–65.8ng/L, 1.73–20ng/L, 1.42–9.52ng/L, 0.64–6.67ng/g (except bacitracin and cloxacillin), 1.33–17.4ng/g (except salinomycin, narasin, monensin, cloxacillin and novobiocin) and 1.50–28.6ng/g (except salinomycin, narasin, monensin and cloxacillin) in surface water, lagoon wastewater, influent, effluent, sediment, manure and sludge, respectively. The developed analytical method was successfully applied in the determination of target compounds in wastewater and sludge samples from Huiyang wastewater treatment plants, and in ground water, lagoon wastewater, manure and sediment collected from a pig farm, in South China. [Copyright &y& Elsevier]

Abstract: A sensitive rapid resolution liquid chromatography–tandem mass spectrometry (RRLC–MS/MS) method, combined with solid-phase extraction, ultrasonic extraction and silica gel cartridge cleanup, was developed for 28 steroids including 4 estrogens (estrone (E1), 17β-estradiol (E2), 17α-ethynyl estradiol (EE2), diethylstilbestrol (DES)), 14 androgens (androsta-1,4-diene-3,17-dione (ADD), 17α-trenbolone, 17β-trenbolone, 4-androstene-3,17-dione, 19-nortestoserone, 17β-boldenone, 17α-boldenone, testosterone (T), epi-androsterone (EADR), methyltestosterone (MT), 4-hydroxy-androst-4-ene-17-dione (4-OHA), 5α-dihydrotestosterone (5α-DHT), androsterone (ADR), stanozolol (S)), 5 progestagens (progesterone (P), ethynyl testosterone (ET), 19-norethindrone, norgestrel, medroxyprogesterone (MP)), and 5 glucocorticoids (cortisol, cortisone, prednisone, prednisolone, dexamethasone) in surface water, wastewater and sludge samples. The recoveries of surface water, influents, effluents and sludge samples were 90.6–119.0% (except 5α-DHT was 143%), 44.0–200%, 60.7–123% and 62.6–138%, respectively. The method detection limits for the 28 analytes in surface water, influents, effluents and freeze-dried sludge samples were 0.01–0.24ng/L, 0.02–1.44ng/L, 0.01–0.49ng/L and 0.08–2.06ng/g, respectively. This method was applied in the determination of the residual steroidal hormones in two surface water of Danshui River, 12 wastewater and 8 sludge samples from two wastewater treatment plants (Meihu and Huiyang WWTPs) in Guangdong (China). Ten analytes were detected in surface water samples with concentrations ranging between 0.4ng/L (17β-boldenone) and 55.3ng/L (5α-DHT); twenty analytes in the wastewater samples with concentrations ranging between 0.3ng/L (P) and 621ng/L (5α-DHT); and 12 analytes in the sludge samples with concentrations ranging between 1.6ng/g (E1) and 372ng/g (EADR). [Copyright &y& Elsevier]

A new and rapid method was developed for simultaneous determination of mangiferin, neomangiferin, timosaponin A-III, and C in Rhizoma Anemarrhenae using rapid resolution liquid chromatography coupled with triple quadrupole mass spectrometry. The analysis was performed on an Eclipse Plus C18 column (I.D. 4.6 × 100 mm, 3.5 μm). Electrospray ionization-tandem interface in the negative mode was employed prior to mass spectrometric detection. Quantitation was based on multiple reaction monitoring (MRM) for determination. Limits of detection (LODs) ranged from 0.7 to 3 pg. The average recoveries ranged from 98.16 to 100.7% with RSDs ≤ 2.03%. The established method was validated, sensitive, and reliable. [ABSTRACT FROM AUTHOR]

Abstract: A simultaneous extraction and analysis method was developed for four classes of antibiotics: sulfonamides (SAs), macrolides (MLs), fluoroquinolones (FQs) and tetracyclines (TCs) in sediment. The antibiotics in the sediment were extracted by using an optimized mixed solution (citric buffer: acetonitrile, 50:50v/v), and analyzed by rapid resolution liquid chromatography–tandem mass spectrometry (RRLC–MS/MS) equipped with electrospray ionization source in the positive mode. The recoveries for the antibiotics in the spiked sediment were: 66.3–123.5%, 48.2–72.0%, 61.8–160.4% and 60.6–151.9% for the SAs, TCs, FQs and MLs, respectively. The LOD ranged from 0.08µg/kg to 4.2µg/kg and LOQ from 0.26µg/kg (erythromycin–H2O) to 14.01µg/kg (norfloxacin). The developed analytical method was applied in the determination of the antibiotics in sediment samples collected from the Pearl Rivers, China. The antibiotics were found at the levels of μg/kg in the sediments of the three rivers. Ofloxacin was found to have the highest concentration of 1560µg/kg in sediment. However, no significant seasonal variation could be found for the antibiotics in the sediments between wet season and dry season. [Copyright &y& Elsevier]

Abstract: (E)-4-hydroxydemethylbromhexine (E-4-HDMB) and (E)-3-hydroxydemethylbromhexine (E-3-HDMB) were found as major metabolites, while (Z)-4-hydroxydemethylbromhexine and (Z)-3-hydroxydemethylbromhexine as minor metabolites of bromhexine in human plasma. These compounds were identified in comparison with synthetic authentic samples. A sensitive and selective rapid resolution liquid chromatography tandem mass spectrometry (RRLC–MS/MS) method was developed to quantify the concentration of bromhexine and its two major metabolites (E-4-HDMB and E-3-HDMB) in human plasma. Following solid phase extraction, the analytes were separated on a Zorbax 1.8μm particle size reversed-phase C18 column, using a gradient elution program with solvents consisting of 0.1% formic acid in acetonitrile and 0.1% formic acid in 5mM ammonium acetate at a flow rate of 0.7mL/min. Detection was carried out with an Agilent 6460 triple-quadrupole mass spectrometer operated with an electrospray ionization source mode operated in the positive ion mode. The recovery of bromhexine, E-4-HDMB, E-3-HDMB, and internal standard (IS) was 63.1–70.9%, 60.5–68.4%, 57.0–63.5%, and 87.8%, respectively. The matrix factors of bromhexine, E-4-HDMB, E-3-HDMB, and IS were 89.9–96.7%, 89.6–94.8%, 90.4–91.4%, and 103%, respectively. After an oral administration of 8.0mg bromhexine to five healthy male subjects, AUC0–24h values of bromhexine, E-4-HDMB, and E-3-HDMB were found to be 93.5±31.9, 34.0±14.5, and 15.8±6.89ngh/mL, respectively; while C max values were 24.6±5.16, 3.11±1.13, and 5.36±2.55ng/mL, respectively. Plasma concentration of bromhexine, E-4-HDMB, and E-3-HDMB declined with t 1/2 which gave 3.6±0.5, 8.4±2.7, and 6.4±2.5h, respectively. [Copyright &y& Elsevier]

Widespread in citrus fruits, naringin, a natural 2,3-dihydroflavonoid, is of particular interest to scientists and has a broad range of beneficial bioactivities to health. Orally administered naringin remains in the gut tract for a relatively long time because of its low bioavailability. Under the metabolism mediated by human gut microbiota, naringin could be an active precursor for derived metabolites to play important physiological roles. However, naringin and its metabolites are hard to accurately quantify due to severe endogenic interference. In this study, an analytical rapid resolution liquid chromatography tandem mass spectrometry (RRLC-MS/MS) method coupled with stable isotope deuterium-labeling is developed and validated to simultaneously quantify naringin as well as its major human gut microbial metabolites naringenin and 3-(4′-hydroxyphenyl) propanoic acid. By eliminating the matrix interferences, this strategy not only confirms naringenin and 3-(4′-hydroxyphenyl) propanoic acid as the predominant metabolites which contribute to the pharmacological effects of naringin but also provides a suitable choice for other flavonoid pharmacokinetics study. [ABSTRACT FROM AUTHOR]

Biqi capsule is a well-known traditional Chinese medicine formula that has been widely applied for the clinical treatment of such diseases as rheumatoid arthritis, scapulohumeral periarthritis and cervical spondylopathy. However, there is concern regarding the toxicity of Biqi capsule owing to its active ingredients, strychnine and brucine. To investigate the toxicokinetics of strychnine and brucine after oral administration of Biqi capsule to rats, a sensitive and simple rapid-resolution liquid chromatography/tandem mass spectrometry method was developed to determine the levels of strychnine and brucine in rat plasma. Chromatographic separation was performed on a Capcell Pak C 18 MG II (3.0 μm, 2.0 × 35 mm) column by gradient elution with acetonitrile and 0.2% formic acid as the mobile phase. The method was validated over the range of 0.25-250 ng/mL for strychnine and 0.025-25 ng/mL for brucine. The intra- and inter-day accuracies of strychnine and brucine in rat plasma were 100.3-106.6 and 90.75-106.1% respectively, and the precisions were within 14.2%. The established method was successfully applied to the toxicokinetic study of strychnine and brucine after single and multiple oral administration of Biqi capsule to male and female rats at 0.4, 0.8 and 1.6 g/kg doses. The results showed different toxicokinetic characteristics in the different groups., (Copyright © 2017 John Wiley & Sons, Ltd.)

To study pharmacokinetic characteristics of epimedin A, B, C and icariin after intermuscular administration of Chuankezhi injection to rat. The established RRLC-MS/MS method was applied for simultaneous determination of four analytes in rat plasma and calculating their pharmacokinetic parameters. As a result, each analyte showed a good linear relationship in the concentration range of 1-1 000 μg•L⁻¹.The intra-day precise was 96.9%-107.5% with RSD<5.99%, inter-day precise was 92.3%-105.0% with RSD<10.16%. The relative recovery of four analytes was 88.1%-101.1% with RSD<7.9% and their absolute recovery was 72.0%-86.6% with RSD<6.3%. After intermuscular administration of Chuankezhi injection, the plasma concentration of four flavonoid glycosides rapidly arose to peaks at about 10 min, and then quickly declined in rat. Tmax of epimedin A, B, C and icariin was 0.21, 0.19, 0.16 and 0.49 h, respectively, and their mean elimination half-life(t1/2z) was 0.60, 0.62, 0.47 and 0.49 h. The established method was validated to be sensitive, rapid and specific for determination of the four analytes. Serum concentration of 4 species of epimedium flavonoids in Chuankezhi injection was low, and their absorption and elimination seem quickly, displaying similar pharmacokinetic characteristics in this study., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)