Quantification of β‐eudesmol in rat plasma using LC–MS/MS and its application to a pharmacokinetic studyJiang, Ligang; Zhang, Chunyang; Li, Haiping
doi: 10.1002/bmc.4023pmid: 28623851
A sensitive and specific LC–MS/MS assay for determination of β‐eudesmol in rat plasma was developed and validated. After liquid–liquid extraction with ethyl ether, the analyte and IS were separated on a Capcell Pak C18 column (50 × 2.0 mm, 5 μm) by isocratic elution with acetonitrile—water–formic acid (77.5:22.5:0.1, v/v/v) as the mobile phase at a flow rate of 0.4 mL/min. An ESI source was applied and operated in positive ion mode; a selected reaction monitoring scan was used for quantification by monitoring the precursor–product ion transitions of m/z 245.1 → 163.1 for β‐eudesmol and m/z 273.4 → 81.2 for IS. Good linearity was observed in the concentration range of 3–900 ng/mL for β‐eudesmol in rat plasma. Intra‐ and inter‐day precision and accuracy were both within ±14.3%. This method was applied for pharmacokinetic studies after intravenous bolus of 2.0 mg/kg or intragastric administration of 50 mg/kg β‐eudesmol in rats.
Development and validation of an LC‐ESI‐MS/MS approach to determine a highly hydrophobic drug, norcantharidin palmitate, and apply to a preliminary pharmacokinetic study in ratsLiu, Xiaolin; Tao, Xiaoguang; Zheng, Qi; Xu, Hang; Zhang, Yu; Lei, Tian; Yin, Tian; He, Haibing; Tang, Xing
doi: 10.1002/bmc.4010pmid: 28500645
In order to investigate the pharmacokinetics of norcantharidin palmitate (NCTD‐PAL) in rats, we developed and validated an LC‐ESI‐MS/MS method. The NCTD‐PAL and internal standard (triamcinoloneacetonide palmitate, TAP) were separated on a Phenomenex Kinetex®XB C18 column, and the mobile phase was composed of tetrahydrofuran (THF)–acetonitrile (20/80, v/v) and an aqueous phase containing 0.2% ammonium hydroxide at a flow rate of 0.3 mL/min. The ESI interface operated in positive mode was used to acquire the mass spectrometric data, and the transition ions were m/z 635.50 → 168.95 and 673.65 → 397.13 for NCTD‐PAL and IS, respectively. The method had a linear range of 10–2000 ng/mL with a correlation coefficient of >0.99. The accuracy (RE, %) was within ±10.1%, and the intra‐ and inter‐day precisions (RSD, %) were 10.9 and 13.8%, respectively. The extraction recovery of NCTD‐PAL at different concentrations ranged from 89.3 to 102.0%. The validated approach was efficaciously applied to a pharmacokinetic study of NCTD‐PAL in rats via intravenous injection. Based on these results obtained, this method is practical and suitable for a wide range of applications.
Development of a validated UPLC–MS/MS method for determination of humantenmine in rat plasma and its application in pharmacokinetics and bioavailability studiesHu, Yanxian; Chen, Minghao; Wang, Zhaoyu; Lan, Yao; Tang, Lan; Liu, Menghua; Zhao, Jie; Hu, Ming; Zhang, Lulu; Ye, Ling
doi: 10.1002/bmc.4017pmid: 28557019
Humantenmine (HMT), the most toxic compound isolated from Gelsemium elegans Benth, is a well‐known active herbal compound. A rapid and sensitive ultra‐performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) method was developed and validated to estimate the absolute oral bioavailability of HMT in rats. Quantification was performed by multiple reaction monitoring using electrospray ionization operated in positive ion mode with transitions of m/z 327.14 → m/z 296.19 for HMT and m/z 323.20 → m/z 236.23 for gelsemine (internal standard, IS). The linear range of the calibration curve was 1–256 nmol/L, with a lower limit of quantification at 1 nmol/L. The accuracy of HMT ranged from 89.39 to 107.5%, and the precision was within 12.24% (RSD). Excellent recovery and negligible matrix effect were observed. HMT remained stable during storage, preparation and analytical procedures. The pharmacokinetics of HMT in rats showed that HMT reached the concentration peak at 12.50 ± 2.74 min with a peak concentration of 28.49 ± 6.65 nmol/L, and the corresponding area under the concentration–time curve (AUC0–t) was 1142.42 ± 202.92 nmol/L min after 200 μg/kg HMT was orally administered to rats. The AUC0–t of HMT given at 20 μg/kg by tail vein administration was 1518.46 ± 192.24 nmol/L min. The calculated absolute bioavailability of HMT was 7.66%.
Study of gliquidone degradation behavior by high‐performance thin‐layer chromatography and ultra‐performance liquid chromatography methodsAbdelwahab, Nada S.; Elsaady, Mohammed T.; Korany, Aml G.; Hegazy, Maha A.
doi: 10.1002/bmc.4025pmid: 28618049
Gliquidone (GQ) is an oral hypoglycemic agent, belonging to second‐generation sulfonylurea derivatives. New high‐performance thin‐layer chromatography (HPTLC) and ultra‐performance liquid chromatography (UPLC) methods have been developed and validated and used for complete stability study of GQ following International Conference on Harmonization guidelines. GQ was subjected to stress and forced degradation under hydrolytic, oxidative and photolytic conditions. The drug was found to be unstable under acidic, alkaline and oxidative conditions with the formation of gliquidone sulfonamide (GQS), while a marked stability was confirmed under thermal and photolytic stress conditions. GQS is the British pharmacopeial impurity A of GQ and also considered as its synthesis intermediate. The developed chromatographic methods have been utilized for anticipating the degradation behavior of GQ under the studied conditions and then used for quantitation of GQ and GQS either in their pure forms or in laboratory prepared mixtures. The methods were successfully applied to GQ in pharmaceutical formulation. The methods have the advantages of being sensitive and less time consuming compared with the reported methods. The obtained results were statistically compared with a reported HPLC method showing no significant difference regarding both accuracy and precision.
The human mast cell line‐1 cell membrane chromatography coupled with HPLC‐ESI‐MS/MS method for screening potentical anaphylactic components from chuanxinlian injectionLin, Yuanyuan; Wang, Cheng; Hou, Yajing; He, Huaizhen; Huang, Limin; Yang, Liu; Sun, Meng
doi: 10.1002/bmc.4015pmid: 28556951
Chuanxinlian injection is a traditional Chinese medicine injection widely used in China to treat sore throat, cough and dysentery, although a high occurrence of severe adverse reactions has been reported in clinical practice in recent years. In the present study, a human mast cell line‐1 cell membrane chromatography coupled with HPLC‐ESI‐MS/MS method was established to screen and identify potentical anaphylactic components in chuanxinlian injection, and the dehydroandrographolide was identified as a potential anaphylactic component. In vitro anaphylactic assay showed that intracellular Ca2+ concentration clearly increased under dehydroandrographolide (100 μm) treatment. β‐Hexosaminidase and histamine release in human mast cell line‐1 cells were both markedly enhanced with increased concentrations of dehydroandrographolide, confirming the anaphylactic activity of dehydroandrographolide. The application for chuanxinlian injection in this study suggested that the developed human mast cell line‐1 cell membrane chromatography coupled with HPLC‐ESI‐MS/MS system may be effective and rapid for screening the potentical anaphylactic components from complex samples.
A platinized stainless steel fiber with in‐situ coated polyaniline/polypyrrole/graphene oxide nanocomposite sorbent for headspace solid‐phase microextraction of aliphatic aldehydes in rice samplesGhiasvand, Alireza; Nasirian, Afagh; Koonani, Samira; Nouriasl, Kolsoum
doi: 10.1002/bmc.4024pmid: 28618092
The surface of a stainless steel fiber was made larger, porous and cohesive by platinizing for tight attachment of its coating. Then it was coated by a polyaniline/polypyrrole/graphene oxide (PANI/PP/GO) nanocomposite film using electrochemical polymerization. The prepared PANI/PP/GO fiber was used for headspace solid‐phase microextraction (HS‐SPME) of linear aliphatic aldehydes in rice samples followed by GC‐FID determination. To achieve the highest extraction efficiency, various experimental parameters including extraction time and temperature, matrix modifier and desorption condition were studied. The linear calibration curves were obtained over the range of 0.05–20 μg g−1 (R2 > 0.99) for C4–C11 aldehydes. The limits of detection were found to be in the range of 0.01–0.04 μg g−1. RSD values were calculated to be <7.4 and 10.7% for intra‐ and inter‐day, respectively. The superiority of the prepared nanocomposite SPME fiber was established by comparison of its results with those obtained by polydimethylsiloxane, carbowax–divinylbenzene, divinylbenzene–carboxen–polydimethylsiloxane and polyacrylate commercial ones. Finally, the nanocomposite fiber was used to extract and determine linear aliphatic aldehydes in 18 rice samples.
Single‐step isolation of embelin using high‐performance countercurrent chromatography and determination of the fatty acid composition of seeds of Embelia schimperiAtlabachew, Minaleshewa; Mehari, Bewketu; Combrinck, Sandra; McCrindle, Robert
doi: 10.1002/bmc.4018pmid: 28557071
Embelin (2,5‐dihydroxy‐3‐undecyl‐p‐benzoquinone) is known for its potent anthelmintic activity, but also for wound‐healing, antidiabetic, anticonvulsant, antitumour, anti‐inflammatory, analgesic, hepatoprotective, antioxidant, antibacterial and antispermatogenic activities. A high‐performance countercurrent chromatography method was developed for the purification of embelin from an extract of the seeds of Embelia schimperi fruit. The optimized solvent system (n‐hexane–ethylacetate–ethanol–water, 7:3:7:3) resulted in the isolation of 13.9 mg of embelin, directly from 100 mg of crude extract, in a single step within a short time (40 min). Although the compound appeared to be completely pure when analysed by ultra‐performance liquid chromatography (UPLC) with photo diode array detection, the purity was established as ~90% by UPLC–mass spectrometry. Furthermore, we report the fatty acid composition of the seeds of E. schimperi fruit. Nine fatty acids were quantified from the fruit seed extract by gas chromatography–mass spectrometry, with linoleic (46.4%), palmitic (21.5%) and oleic (19.6%) acids making up the largest proportions.