37 results on '"Liquid chromatography–mass spectrometry"'
Search Results
2. Capillary ultra performance liquid chromatography–tandem mass spectrometry analysis of tienilic acid metabolites in urine following intravenous administration to the rat.
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King, Adam M., Grant, Isobelle, Rainville, Paul D., Isaac, Giorgis, Coen, Muireann, Wilson, Ian D., and Plumb, Robert S.
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DIURETICS , *LIQUID chromatography-mass spectrometry , *DRUG metabolism , *DRUG administration , *LABORATORY rats , *THERAPEUTICS - Abstract
Capillary scale (100 mm × 150 μm id) UPLC/MS/MS, performed using reversed-phase gradient chromatography on sub 2 μm particles, has been successfully employed for the characterization of the metabolites of the drug tienilic acid (TA) excreted via the urine following oral administration to the rat. The capillary LC system provided a significant increase (range ca. 11–33-fold) in sensitivity compared with a conventional 150 mm × 2.1 mm id UPLC system. An investigation of the effect of the injection volume and sample mass loading on the capillary column on the results obtained for both endogenous metabolites and TA was performed. This demonstrated that the injection of up to 2 μL of rat urine onto the system was permitted whilst still providing excellent chromatographic results and robustness. Qualitative analysis of the urine revealed the presence of TA itself and a total of 15 metabolites of the drug, including those resulting from biotransformations such as hydroxylation or conjugation. The capillary chromatography system was shown to be robust, and capable of providing comprehensive drug metabolite profiles from small format urine samples such as those obtained from preclinical studies in rodents. [ABSTRACT FROM AUTHOR]
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- 2018
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3. Validation of an LC-MS/MS method for simultaneous quantification of venlafaxine and its five metabolites in rat plasma and its application in a pharmacokinetic study.
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Gu, Guodong, Black, Michelle, Cookson, Colt, Fiorella, Anna, Li, Yinghe, Gorman, Steven H., and Bakhtiar, Ray
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VENLAFAXINE , *LIQUID chromatography-mass spectrometry , *BLOOD plasma , *PHARMACOKINETICS , *LABORATORY rats , *THERAPEUTICS - Abstract
A sensitive, selective, and reliable LC-MS/MS method was developed and validated for simultaneous quantification of venlafaxine (VEN) and its 5 metabolites (ODV, NDV, NNDDV, OHV and NODDV) in rat plasma. The calibration ranges are 15.0 to 6000 ng/mL for VEN, 1.00 to 400 ng/mL for ODV, 5.00 to 2000 ng/mL for NDV, 1.00 to 400 ng/mL for NNDDV, 10.0 to 4000 ng/mL for OHV, and 0.200 to 20.0 ng/mL for NODDV. Briefly, 50 μL of rat plasma was extracted using liquid-liquid extraction (LLE) with methyl tert -butyl ether (MTBE). The analytes were separated on an Agilent SB-Phenyl (50 mm × 4.6 mm, 3.5 μm) column using a binary gradient of 0.1% formic acid in water versus 0.1% formic acid in acetonitrile at a flow rate of 0.8 mL/min. The method was validated following FDA guidance for bioanalytical method validation. Validated method was successfully applied to a pharmacokinetic study of VEN orally administered to rats. [ABSTRACT FROM AUTHOR]
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- 2018
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4. Development of a liquid chromatography–tandem mass spectrometry method for simultaneous determination of five isoflavonoids and seven neurochemicals in rat brain dialysate and its application to a pharmacological study.
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Xiao, Bingxin, Dong, Jie, Yan, Mingzhu, Liu, Yun, Li, Yanli, Yang, Guangsheng, and Sun, Zengxian
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LIQUID chromatography-mass spectrometry , *ISOFLAVONOIDS , *PUERARIA , *MEDICINAL plants , *PHARMACOLOGY , *LABORATORY rats , *THERAPEUTICS - Abstract
Abstract: Pueraria lobata is a medicinal plant widely used in traditional Chinese medicine. The total pueraria isoflavones have demonstrated positive effect against neurological disorders. In the present study, we first develop an ultra high performance liquid chromatography and tandem mass spectrometry method to quantify the multiple active pueraria isoflavonoids and neurochemical markers in brain dialysate to provide tools for further exploring the functional mechanism of pueraria isoflavones for neuroactivities. A phenomenex Luna C18 column (50 × 2.0 mm, 5 μm) was employed with acetonitrile/0.05% formic acid in water as the mobile phase for the separation of analytes. A mass spectrometer with electrospray ionization source in positive/negative ion switching mode was used for multiple reaction monitoring of the detected compounds. The method was validated and proved acceptable. The intra‐ and interday precision across quality control levels was within 13.87 for all analytes, whereas the deviation of assay accuracies ranged between 0.03 and 11.53%. The method was successfully applied to a pharmacological study of pueraria isoflavones in rat brain. [ABSTRACT FROM AUTHOR]
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- 2018
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5. Drug--Drug Interactions Between PA-824 and Darunavir Based on Pharmacokinetics in Rats by LC--MS-MS.
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Libin Wang, Jun Zhao, Ruitao Zhang, Le Mi, Xin Shen, Nan Zhou, Tian Feng, Juan Jing, Xueying Liu, and Shengyong Zhang
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THERAPEUTICS , *HIV infections , *DRUG interactions , *TUBERCULOSIS treatment , *DARUNAVIR , *PHARMACOKINETICS , *LABORATORY rats , *LIQUID chromatography-mass spectrometry , *PROTEASE inhibitors - Abstract
Currently, patients with co-infection with HIV and tuberculosis are treated with more than one drug. PA-824 a new chemical entity and a member of a class of compounds known as nitroimidazo-oxazines, has significant antituberculosis activity and a unique mechanism of action. Darunavir (Prezista™) is a new protease inhibitor of HIV-1. A simple, sensitive and rapid LC-MSMS method has been developed and validated for simultaneous determination of PA-824 and darunavir. Chromatographic separation was achieved on Agilent Eclipse plus C18 column (100mm x 2.1 mm, 3.5 µm) using gradient elution of acetonitrile--water (90:10, v/v) with fast gradient elution at a flow rate of 0.6 mL/min and run time of 4.5 min. The mass spectrometer was run in positive electrospray ionization mode using multiple reaction monitoring to monitor the mass transitions. The method was validated for accuracy, precision, linearity, range, selectivity, lower limit of quantification, recovery and matrix effect. All validation parameters met the acceptance criteria according to regulatory guidelines. The method had been successfully applied to a pharmacokinetic study of fixed dose administration of PA-824, darunavir and their combination in rats. The results indicated that when co-administration of darunavir could decrease the amount of PA-824 in vivo and extend the elimination half-life. [ABSTRACT FROM AUTHOR]
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- 2018
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6. Comparative pharmacokinetics of triterpenic acids in normal and immunosuppressed rats after oral administration of Jujubae Fructus extract by UPLC-MS/MS.
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Li, Yao, Guo, Sheng, Hua, Tingting, Wang, Yanyan, Wei, Dandan, Zhao, Ming, Su, Shulan, and Duan, Jin-ao
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INDIAN jujube , *TRITERPENES , *PHARMACOKINETICS , *IMMUNOSUPPRESSION , *LIQUID chromatography-mass spectrometry , *LABORATORY rats , *THERAPEUTICS - Abstract
The fruit of Ziziphus jujuba ( Jujubae Fructus ) has been used as food and crude drug for thousands of years. Although several chemical and biological studies have revealed triterpenic acid as the main bioactive constituent of Jujubae Fructus responsible for immune-regulatory activity, only few pharmacokinetic studies have been conducted. To comprehend the kinetics of triterpenic acids and promote their curative application, a sensitive and efficient ultra-performance liquid chromatography coupled with mass spectrometry method (UPLC-MS/MS) was established. UPLC-MS/MS was applied for the simultaneous determination of ceanothic acid, epiceanothic acid, pomonic acid, alphitolic acid, maslinic acid, betulinic acid, and betulonic acid in normal and immunosuppressed rat plasma samples. After sample preparation, chromatographic separation was performed on an Acquity UPLC BEH C 18 column (2.1 × 100 mm, 1.7 μm) with acetonitrile: methanol (1:1, v/v) and 0.5% ammonium acetate in water as mobile phase. The established method was validated and found to be specific, accurate, and precise for the seven triterpenic acids, and was successfully applied for the pharmacokinetic study of rat plasma samples. The results showed that the pharmacokinetic parameters (C max , T max , AUC 0–t , AUC 0–∞, and CLz/F) in the plasma samples of immunosuppressed rats were significantly different from those in normal rats, and might provide an insight for the clinical usage of triterpenic acids from Jujubae Fructus . [ABSTRACT FROM AUTHOR]
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- 2018
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7. Accurate quantification of PGE2 in the polyposis in rat colon (Pirc) model by surrogate analyte-based UPLC–MS/MS.
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Yun, Changhong, Dashwood, Wan-Mohaiza, Kwong, Lawrence N., Gao, Song, Yin, Taijun, Ling, Qinglan, Singh, Rashim, Dashwood, Roderick H., and Hu, Ming
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DINOPROSTONE , *ADENOMATOUS polyposis coli , *LABORATORY rats , *CIRCULATING anticoagulants , *LIQUID chromatography-mass spectrometry , *TANDEM mass spectrometers , *THERAPEUTICS - Abstract
An accurate and reliable UPLC–MS/MS method is reported for the quantification of endogenous Prostaglandin E2 (PGE 2 ) in rat colonic mucosa and polyps. This method adopted the “surrogate analyte plus authentic bio-matrix” approach, using two different stable isotopic labeled analogs — PGE 2 -d9 as the surrogate analyte and PGE 2 -d4 as the internal standard. A quantitative standard curve was constructed with the surrogate analyte in colonic mucosa homogenate, and the method was successfully validated with the authentic bio-matrix. Concentrations of endogenous PGE 2 in both normal and inflammatory tissue homogenates were back-calculated based on the regression equation. Because of no endogenous interference on the surrogate analyte determination, the specificity was particularly good. By using authentic bio-matrix for validation, the matrix effect and exaction recovery are identically same for the quantitative standard curve and actual samples – this notably increased the assay accuracy. The method is easy, fast, robust and reliable for colon PGE 2 determination. This “surrogate analyte” approach was applied to measure the Pirc (an Apc -mutant rat kindred that models human FAP) mucosa and polyps PGE 2 , one of the strong biomarkers of colorectal cancer. A similar concept could be applied to endogenous biomarkers in other tissues. [ABSTRACT FROM AUTHOR]
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- 2018
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8. Elucidation of mechanism of Si-jun-zi decoction-induced reversal of spleen deficiency syndrome in rats by LC-QTOF/MS metabolomics.
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Qinghua Yan, Huili Mao, and Yanming Wei
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SPLEEN diseases , *CHINESE medicine , *METABOLOMICS , *LIQUID chromatography-mass spectrometry , *AMYLASES , *BIOMARKERS , *LABORATORY rats , *THERAPEUTICS - Abstract
Purpose: To explore the therapeutic effect and mechanism of action of Si-jun-zi decoction (SJZD) in rat spleen deficiency syndrome. Methods: Spleen deficiency syndrome was induced in a rat model with reserpine. Liquid chromatography quadrupole time-of-flight mass spectrometry (LC-Q-TOF/MS) and partial least squaresdiscriminate models (PLS-DA) were used to analyze the difference in global metabolite profile within all groups. Variable importance projection (VIP > 1) and Student's t-test (p < 0.05) were used for biomarker selection. Results: Enzymatic results showed that the level of amylase (AMY), pepsin (LPS) and pepsase were significantly lower in the untreated rats than in normal control rats and SJZD group rats (P < 0.05). Histopathological analysis showed there were significant pathological changes in the untreated rats compared with the normal control group and SJZD group rats. PLS-DA score plots of the untreated group rats clustered separately from control rats, whereas SJZD group rats clustered closely to normal control rats. Twenty potential biomarkers, including phospholipid and fatty acids, were screened. The relative content of 20 metabolites showed significant differences in the untreated group compared with control and SJZD groups (p < 0.05). Six potentially perturbed metabolic pathways were found, which might be potential targets pathways for SJZD intervention in spleen deficiency syndrome. Conclusion: Metabolomics approach is an effective tool for understanding the therapeutic mechanisms of SJZD. [ABSTRACT FROM AUTHOR]
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- 2017
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9. A validated LC–MS/MS method for the estimation of glimepiride and pitavastatin in rat plasma: Application to drug interaction studies.
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Surendran, Shruti, Paul, David, Sushmita, Ratna, Krishna, Lavanya, Tiwari, Nirbhay Kumar, Giri, Sanjeev, and Satheeshkumar, Nanjappan
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STATINS (Cardiovascular agents) , *LIQUID chromatography-mass spectrometry , *DRUG interactions , *LABORATORY rats , *DYSLIPIDEMIA , *THERAPEUTICS - Abstract
Glimepiride (GLI) is prescribed for the management of type-2 diabetes where as pitavastatin (PIT) for the treatment of diabetes associated dyslipidemia. Both the drugs are metabolized by CYP2C9 and have the potential of altering the enzyme through either inhibition or induction. In this respect, we present a simple, fast and validated bioanalytical LC–MS/MS method for the simultaneous estimation of GLI and PIT from rat plasma. Waters XTerra RP HPLC column (4.6 × 100 mm, 5 μm) with mobile phase consisting of acetonitrile and 10 mM ammonium acetate (pH-6.0) in the ratio 85:15 ( v/v ) at a flow rate of 1 mL/min was used for the chromatographic separation. The negative ionization mode with MRM transitions: m / z 420.17 → 288.13 for PIT, m / z 489.59 → 350.12 for GLI and m / z 380.08 → 316.31for celecoxib as internal standard (IS). A total run time of 3 min and LLOQ was found to be 5 ng/mL for both PIT and GLI. The method was applied to study the drug interaction between GLI and PIT in rat liver microsomes. In vivo rat pharmacokinetics study showed there was a 1.29-fold increase in AUC 0-∞ and 1.2-fold decrease in the clearance of PIT in presence of GLI. No notable difference in the pharmacokinetic profile of GLI was observed upon the intravenous co-administration of PIT. [ABSTRACT FROM AUTHOR]
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- 2017
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10. Sensitive analysis and simultaneous assessment of pharmacokinetic properties of crocin and crocetin after oral administration in rats.
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Zhang, Yue, Fei, Fei, Zhen, Le, Zhu, Xuanxuan, Wang, Jiankun, Li, Sijia, Geng, Jianliang, Sun, Runbin, Yu, Xiaoyi, Chen, Tingting, Feng, Siqi, Wang, Pei, Yang, Na, Zhu, Yejin, Huang, Jingqiu, Zhao, Yuqing, Aa, Jiye, and Wang, Guangji
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CROCIN , *CAROTENOIDS , *PHARMACOKINETICS , *ORAL medication , *LIQUID chromatography-mass spectrometry , *LABORATORY rats , *THERAPEUTICS - Abstract
Crocin and crocetin in rat plasma were simultaneously analysed using ultra-performance liquid chromatography tandem mass spectroscopy (UPLC–MS/MS), and method was fully validated. For the first time, levels of both crocin and crocetin in plasma were profiled after oral administration of crocin, and this UPLC–MS/MS approach was applied to evaluate pharmacokinetics and relative bioavailability of crocin and crocetin in rats. It was shown that crocin transformed into crocetin quickly in the gastrointestinal tract, and crocetin was 56–81 fold higher exposed in rat plasma than crocin after oral administration of crocin. A comparison study revealed that an oral administration of equal molar crocin achieved higher exposure of crocetin in rat plasma than that of crocetin. It was suggested that oral administration of crocin has the advantages over crocetin, and crocetin may be the active component potentially responsible for the pharmacological effect of crocin. [ABSTRACT FROM AUTHOR]
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- 2017
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11. Simultaneous determination of anemoside B4, phellodendrine, berberine, palmatine, obakunone, esculin, esculetin in rat plasma by UPLC–ESI–MS/MS and its application to a comparative pharmacokinetic study in normal and ulcerative colitis rats.
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Yang, Lianrong, Meng, Xin, Yu, Xiaojin, and Kuang, Haixue
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BERBERINE , *COLITIS treatment , *ULCERATIVE colitis , *BLOOD plasma , *LIQUID chromatography-mass spectrometry , *PHARMACOKINETICS , *LABORATORY rats , *COMPARATIVE studies , *THERAPEUTICS - Abstract
A sensitive and rapid ultra-performance liquid chromatography-electrospray ionization-mass spectrometry (UPLC–ESI–MS/MS) method was developed for the simultaneous analysis of anemoside B4, phellodendrine, berberine, palmatine, obakunone, esculin, esculetin, toosendanin (IS 1 of anemoside B4), tetrahydropalmatine (IS 2 of phellodendrine, berberine, palmatine and obakunone) and scopoletin (IS 3 of esculin and esculetin) and to compare the pharmacokinetics of these active ingredients in normal and ulcerative colitis rats. After methanol deproteinization, solvents were evaporated at 40 °C under a gentle stream of nitrogen. Chromatography was performed using a C18 column with a gradient elution of 0.1% aqueous formic acid and acetonitrile at 0.4 ml/min. Detection and measurement were performed on a 4000 QTRAP UPLC–MS/MS system from AB Sciex in the multiple reaction monitoring (MRM) mode. Phellodendrine, berberine, palmatine, obakunone, esculin, esculetin, tetrahydropalmatine (IS 2 ) and scopoletin (IS 3 ) were monitored under positive ionization conditions. Anemoside B4, and toosendanin (IS 1 ) were monitored under negative ionization conditions. The optimized mass transition ion-pairs ( m / z ) were 1221.1/750.7 for anemoside B4, 343.2/193.2 for phellodendrine, 337.1/321.0 for berberine, 353.0/336.9 for palmatine, 455.1/161.1 for obakunone, 341.2/179.2 for esculin, 179.1/123.0 for esculetin, 573.4/531.4 for toosendanin (IS 1 ), 356.2/192.2 for tetrahydropalmatine (IS 2 ) and 193.0/133.1 for scopoletin (IS 3 ). [ABSTRACT FROM AUTHOR]
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- 2017
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12. Liquid chromatography-tandem mass spectrometric determination of propofol in rat serum and hair at attogram level after derivatization with 3-bromomethyl-propyphenazone.
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Khedr, Alaa, El-Hay, Soad S.Abd, and Kammoun, Ahmed K.
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LIQUID chromatography-mass spectrometry , *PROPOFOL , *EXTRACTION techniques , *SENSITIVITY analysis , *BIOLOGICAL assay , *LABORATORY rats , *THERAPEUTICS - Abstract
A sensitive, selective and precise liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for determination of propofol (PRO) in rat serum and hair has been developed. 3-Bromomethyl-propyphenazone was used as derivatization reagent forming propofol-methyl-propyphenazone compound. The derivatization reaction was optimized and validated for maximum MS sensitivity. The MS instrumental sensitivity reached to 10 attogram. The serum samples were extracted by using Chromabond C 8 columns, while hair samples extracted with methanol. The tendency of volatility of PRO was minimized by adding triethylamine to the extract before the use of nitrogen gas for evaporation of solvent. The limit of quantitation (LLOQ) was 0.01 pg/mL and the assay was linear to 10000 pg/mL. The intra-and inter-day precision (RSD%) ranged from 0.33 to 3.44% while the accuracy (E r %, relative error) were −6.4 to 1.1%. The ionization suppression, due to reagent, was minimized by reacting the excess reagent with methanol, and eluting to waste before MS ionization source (2–4.5 min). The method was successfully applied for detection and determination of PRO in rat serum and hair after 7–28 days from administration of only one dose of propofol (10 mg/kg). [ABSTRACT FROM AUTHOR]
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- 2017
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13. Development and validation of ultrafast LC–MS/MS method for quantification of anti-influenza agent camphecene in whole rat blood using dried blood spots and its application to pharmacokinetic studies.
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Rogachev, Artem D., Yarovaya, Olga I., Ankov, Sergey V., Khvostov, Mikhail V., Tolstikova, Tatyana G., Pokrovsky, Andrey G., and Salakhutdinov, Nariman F.
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LIQUID chromatography-mass spectrometry , *INFLUENZA treatment , *DRIED blood spot testing , *PHARMACOKINETICS , *LABORATORY rats , *CAMPHOR , *THERAPEUTICS - Abstract
A fast, selective and sensitive procedure for quantitation of the camphor-based anti-influenza agent camphecene in whole rat blood was developed and validated using dried blood spots and LC–MS/MS. The method was validated according to recommendations of the FDA and EMA in terms of selectivity, linearity, accuracy, precision, recovery, matrix factor, stability, and carry-over. Sample preparation included spotting 20 μL of whole blood taken from the tail vein onto the paper, drying and extracting the analyte, followed by evaporation of the solvent and analysis of the residue. HPLC separations were run on a reversed-phase microcolumn; the time of analysis was less than 2 min. MS/MS detection was performed on a triple quadrupole mass-spectrometer using multiple reaction monitoring (MRM) mode. Transitions 196.4 → 122.2/153.3 and 152.2 → 93.1/107.2 were monitored for camphecene and 2-adamantylamine hydrochloride (internal standard), respectively. The intra- and inter-day precisions and accuracies, matrix factor, carry-over and recovery were within acceptable limits. Despite low extraction recovery (less than 2%), the sensitivity of the method was enough to detect the analyte in the concentration range 50–2500 ng/mL. The application of the method was shown in pharmacokinetic studies of camphecene in rats at a dose of 10 mg/kg. [ABSTRACT FROM AUTHOR]
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- 2016
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14. Simultaneous determination of erlotinib and tamoxifen in rat plasma using UPLC–MS/MS: Application to pharmacokinetic interaction studies.
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Maher, Hadir M., Alzoman, Nourah Z., and Shehata, Shereen M.
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ERLOTINIB , *TAMOXIFEN , *PHARMACOKINETICS , *DRUG interactions , *BLOOD plasma , *LIQUID chromatography-mass spectrometry , *LABORATORY rats , *THERAPEUTICS - Abstract
Tamoxifen (TAM) is a non-steroidal estrogen receptor antagonist that enhances erlotinib (ERL)-induced cytotoxicity in the treatment of NSCLC. ERL and TAM are metabolized by CYP3A4 enzymes. In addition, both drugs have the potential of altering the enzymatic activity through either inhibition (ERL) or induction (TAM). Thus it was expected that pharmacokinetics (PK) drug–drug interactions (DDIs) could be encountered following their co-administration. In this respect, a bioanalytical UPLC–MS/MS method has been developed and validated for the simultaneous determination of ERL and TAM in rat plasma samples, using ondansetron (OND) as an internal standard (IS). Plasma samples were prepared using mixed mode cationic solid phase extraction (SPE) STRATA™ −X-C 33 μm cartridges with good extraction recovery of both drugs from rat plasma (E r % from −13.92 to −3.32). The drugs were separated on a Waters BEH™ C18 column with an isocratic elution using a mobile phase composed of a mixture of acetonitrile and water, each with 0.15% formic acid, in the ratio of 80: 20, v/v. Quantitation was carried out using the positive ionization mode with multiple reaction monitoring (MRM) at m / z 394.20 > 278.04 (ERL), m / z 372.25 > 72.01 (TAM), and m / z 294.18 > 170.16 (OND). The method was fully validated as per the FDA guidelines over the concentration range of 0.2–50 ng/mL with very low lower limit of quantification (LLOQ) of 0.2 ng/mL for both ERL and TAM. The intra- and inter-day assay precision (in terms of relative standard deviation, RSD) and accuracy (in terms of percentage relative error, % E r ) were evaluated for both drugs and the calculated values evaluated at four different concentration levels were within the acceptable limits (<15%) for concentrations other than LLOQ and 20% for LLOQ. The method was successfully applied to the study of possible PK-DDI following the oral administration of ERL and TAM in a combination, compared to their single administration. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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15. Female Flinders Sensitive Line rats show estrous cycle-independent depression-like behavior and altered tryptophan metabolism.
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Eskelund, Amanda, Budac, David P., Sanchez, Connie, Elfving, Betina, and Wegener, Gregers
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MENTAL depression , *THERAPEUTICS , *ESTRUS , *TRYPTOPHAN metabolism , *LABORATORY rats , *LIQUID chromatography-mass spectrometry - Abstract
Clinical studies suggest a link between depression and dysfunctional tryptophan (TRP) metabolism. Even though depression is twice as prevalent in women as men, the impact of the estrous cycle on TRP metabolism is not well-understood. Here we investigated 13 kynurenine and serotonin metabolites in female Flinders Sensitive Line (FSL) rats, a genetic rat model of depression. FSL rats and controls (Flinders Resistant Line rats), 12–20 weeks old, were subject to the forced swim test (FST), a commonly used measure of depression-like behavior. Open field was used to evaluate locomotor ability and agoraphobia. Subsequently, plasma and hemispheres were collected and analyzed for their content of TRP metabolites using liquid chromatography-tandem mass spectrometry. Vaginal saline lavages were obtained daily for ⩾2 cycles. To estimate the effects of sex and FST we included plasma from unhandled, naïve male FSL and FRL rats. Female FSL rats showed a depression-like phenotype with increased immobility in the FST, not confounded by anxiety. In the brain, 3-hydroxykynurenine was increased whereas anthranilate and 5-hydroxytryptophan were decreased. In plasma, anthranilate and quinolinate levels were lower in FSL rats compared to the control line, independent of sex and FST. The estrous cycle neither impacted behavior nor TRP metabolite levels in the FSL rat. In conclusion, the female FSL rat is an interesting preclinical model of depression with altered TRP metabolism, independent of the estrous cycle. The status of the pathway in brain was not reflected in the plasma, which may indicate that an inherent local, cerebral regulation of TRP metabolism occurs. [ABSTRACT FROM AUTHOR]
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- 2016
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16. An HPLC–MS method for the quantification of new acetylcholinesterase inhibitor PC 48 (7-MEOTA-donepezil like compound) in rat plasma: Application to a pharmacokinetic study.
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Mzik, Martin, Korabecny, Jan, Nepovimova, Eugenie, Voříšek, Viktor, Palička, Vladimir, Kuca, Kamil, and Zdarova Karasova, Jana
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LIQUID chromatography-mass spectrometry , *ACETYLCHOLINESTERASE inhibitors , *BLOOD plasma , *PHARMACOKINETICS , *ALZHEIMER'S disease treatment , *DONEPEZIL , *LABORATORY rats , *THERAPEUTICS - Abstract
A simple, rapid and sensitive method based on liquid chromatography–tandem mass spectrometry (LC–MS/MS) has been developed and validated for the quantitative determination in rat plasma of a new candidate for AD treatment, namely PC 48 (a 7-MEOTA-donepezil like compound) in rat plasma. Sample preparation involved pH adjustment with sodium hydroxide followed by solvent extraction with ethyl acetate:dichloromethane (80:20, v/v). The chromatographic separation was achieved on an Ascentis Express RP-Amide column (75 mm × 2.1 mm, 2.7 μm) with a gradient mobile phase consisting of 0.05 M aqueous formic acid and acetonitrile. Detection was carried out using positive-ion electrospray tandem mass spectrometry on an LTQ XL system using the MS/MS CID (collision-induced dissociation) mode. The method was linear in the range 0.1–1000 ng/ml (r 2 = 0.999) with a lower limit of quantitation of 0.1 ng/mL. Extraction recovery was in the range 63.5–72.1% for PC 48 and 70.5% for reserpine (internal standard, IS). Intra- and inter-day precisions measured as relative standard deviation were below 10.8% and accuracy was from −7.2% to 7.4%. The method was successfully applied to a pharmacokinetic study involving intramuscular application of 3.86 mg/kg PC 48 to rats for the first time. Pharmacokinetic parameters for PC 48 include C max 39.09 ± 4.45 ng/mL, T max 5.00 ± 3.08 min, AUC 0 − t 23374 ± 4045 min ng/mL and t 1/2 1065 ± 246 min. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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17. NecroX-5 protects mitochondrial oxidative phosphorylation capacity and preserves PGC1α expression levels during hypoxia/reoxygenation injury.
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Vu Thi Thu, Hyoung Kyu Kim, Le Thanh Long, Bayalagmaa Nyamaa, In-Sung Song, To Thanh Thuy, Nguyen Quang Huy, Jubert Marquez, Soon Ha Kim, Nari Kim, Kyung Soo Ko, Byoung Doo Rhee, and Jin Han
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PHYSIOLOGICAL effects of antioxidants , *OXIDATIVE phosphorylation , *CARDIOTONIC agents , *HYPOXEMIA , *LABORATORY rats , *LIQUID chromatography-mass spectrometry , *THERAPEUTICS - Abstract
Although the antioxidant and cardioprotective effects of NecroX-5 on various in vitro and in vivo models have been demonstrated, the action of this compound on the mitochondrial oxidative phosphorylation system remains unclear. Here we verify the role of NecroX-5 in protecting mitochondrial oxidative phosphorylation capacity during hypoxia-reoxygenation (HR). Necrox-5 treatment (10 μM) and non-treatment were employed on isolated rat hearts during hypoxia/ reoxygenation treatment using an ex vivo Langendorffsystem. Proteomic analysis was performed using liquid chromatography-mass spectrometry (LC-MS) and non-labeling peptide count protein quantification. Real-time PCR, western blot, citrate synthases and mitochondrial complex activity assays were then performed to assess heart function. Treatment with NecroX-5 during hypoxia significantly preserved electron transport chain proteins involved in oxidative phosphorylation and metabolic functions. NecroX-5 also improved mitochondrial complex I, II, and V function. Additionally, markedly higher peroxisome proliferator-activated receptorgamma coactivator-1α (PGC1α) expression levels were observed in NecroX-5-treated rat hearts. These novel results provide convincing evidence for the role of NecroX-5 in protecting mitochondrial oxidative phosphorylation capacity and in preserving PGC1α during cardiac HR injuries. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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18. Simultaneous determination of nintedanib and its metabolite by UPLC–MS/MS in rat plasma and its application to a pharmacokinetic study.
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Lin, Dan, Qiao, Li-man, Zhang, Yu-niao, Liu, Yuan, and Liu, Xin-she
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IDIOPATHIC pulmonary fibrosis , *LIQUID chromatography-mass spectrometry , *METABOLITES , *DIAZEPAM , *GRADIENT elution (Chromatography) , *PHARMACOKINETICS , *PLASMA chemistry , *LABORATORY rats , *THERAPEUTICS - Abstract
To establish a rapid and sensitive ultra performance liquid chromatography tandem mass spectrometry (UPLC–MS/MS) method for the determination of concentration of nintedanib and its metabolite BIBF 1202 in rat plasma. The nintedanib and its metabolite and the internal standard (diazepam) were separated on an Acquity UPLC BEH C18 chromatography column (2.1 mm × 50 mm, 1.7 μm) using gradient elution with a mobile phase of acetonitrile and 0.1% formic acid in water at a flow rate of 0.30 mL/min. The detection was performed on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring (MRM) mode to monitor the precursor-to-product ion transitions of m / z 540.3 → 113.1 for nintedanib, m / z 526.3 → 113.0 for BIBF 1202 and m / z 285.3 → 193.1 for diazepam (IS) using a positive electrospray ionization interface. The method was validated for 1.0–200 ng/mL for nintedanib and 0.5–100 ng/mL for BIBF 1202 using 100 μL of plasma sample. Total time for each chromatograph was 3.0 min. The intra- and inter-day precision and accuracy of the quality control samples at low, medium, and high concentration levels exhibited relative standard deviations (RSD) <10.8% and the accuracy values ranged from −11.9% to 10.4%. The method was successfully applied to a pharmacokinetic study of nintedanib and BIBF 1202 in rats after oral administration of nintedanib. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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- View/download PDF
19. Simultaneous determination of doxorubicin and curcumin in rat plasma by LC–MS/MS and its application to pharmacokinetic study.
- Author
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Ma, Wenzhuan, Wang, Jinling, Guo, Qiang, and Tu, Pengfei
- Subjects
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DOXORUBICIN , *CURCUMIN , *BLOOD plasma , *LABORATORY rats , *LIQUID chromatography-mass spectrometry , *PHARMACOKINETICS , *THERAPEUTICS - Abstract
A specific, sensitive and rapid liquid chromatography tandem mass spectrometry (LC–MS/MS) method has been developed and validated for simultaneous quantification of doxorubicin and curcumin in rat plasma after intravenous administration. The analytes of doxorubicin and curcumin were extracted with methanol precipitation using glibenclamide as internal standard (IS). The chromatographic separation was performed on a C 18 column with acetonitrile and 0.1% formic acid water as mobile phase and with gradient elution at a flow rate of 0.2 mL/min. Calibration curves were linear over the ranges of 2–8000 ng/mL for doxorubicin and 5–2000 ng/mL for curcumin ( r > 0.99). The lower limit of quantification (LLOQ) was 2 ng/mL for DOX and 5 ng/mL for Cur. Finally, this developed method was successfully applied in the pharmacokinetic study of doxorubicin and curcumin in rats and evaluated the effects of curcumin on the absorption of doxorubicin after intravenous administration. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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- View/download PDF
20. Simultaneous determination of six flavonoids from Paulownia tomentosa flower extract in rat plasma by LC–MS/MS and its application to a pharmacokinetic study.
- Author
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Dai, Bin, Hu, Zhiqiang, Li, Haiyan, Yan, Chong, and Zhang, Liwei
- Subjects
- *
FLAVONOIDS , *BLOOD plasma , *PAULOWNIA tomentosa , *LIQUID chromatography-mass spectrometry , *LABORATORY rats , *PHARMACOKINETICS , *ELECTROSPRAY ionization mass spectrometry , *THERAPEUTICS - Abstract
A simple, rapid and sensitive liquid chromatography–tandem mass spectrometry (LC–MS/MS) method was developed and validated for simultaneous determination of six components including apigenin, quercetin, apigenin-7- O -β- d -glucoside, quercetin-3- O -β- d -glucoside, 3′-methoxyluteolin-7- O -β- d -glucoside, and tricin-7- O -β- d -glucopyranoside in rat plasma using formononetin as the internal standard (IS). The plasma samples were pretreated by a one-step liquid–liquid extraction with dichloromethane. The chromatographic separation was carried out on a ZORBAX SB-Aq column with a gradient mobile phase consisting of acetonitrile and 2 mM aqueous ammonium acetate. All analytes and IS were quantitated through electrospray ionization in negative ion multiple reaction monitoring mode. The mass transitions were as follows: m / z 269.1 → 117.2 for apigenin, m / z 301.2 → 151.2 for quercetin, m / z 431.3 → 311.2 for apigenin-7- O -β- d -glucoside, m / z 463.2 → 300.2 for quercetin-3- O -β- d -glucoside, m / z 461.3 → 283.1 for 3′-methoxyluteolin-7- O -β- d -glucoside, m / z 491.3 → 313.1 for tricin-7- O -β- d -glucopyranoside, and m / z 267.2 → 252.2 for IS, respectively. All calibration curves exhibited good linearity with correlation coefficient ( r ) > 0.995. The intra-day and inter-day precisions (RSD) at three QC levels were both less than 14.0% and the accuracies ranged from 89.8% to 113.8%. The extraction recoveries of six compounds ranged from 82.3% to 92.5%. The validated method was successfully applied to pharmacokinetic study of the six components in male rat plasma after oral administration of Paulownia tomentosa flower extract. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
21. A sensitive method for digoxin determination using formate-adduct ion based on the effect of ionization enhancement in liquid chromatograph–mass spectrometer.
- Author
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Li, Xia, Wang, Yu, Zhou, Qingyuan, Yu, Yunqiu, Chen, Lihong, and Zheng, Jie
- Subjects
- *
DIGOXIN , *LIQUID chromatography-mass spectrometry , *LABORATORY rats , *DRUG administration , *STEROID saponins , *FORMIC acid , *THERAPEUTICS - Abstract
A sensitive and rapid method based on formate-adduct ion detection was developed and fully validated for digoxin determination in rat plasma. For LC/MS/MS detection with formate-adducts as precursor ions, transitions of m / z 825.5 → 779.9 for digoxin and m / z 809.5 → 763.4 for the internal standard (digitoxin) were monitored in negative mode. To investigate the impact of formic acid on the mass response and method sensitivity, a formic acid concentration range of 0–0.1% (0, 0.0005%, 0.002%, 0.01%, 0.1%, v/v) was evaluated. A concentration of 0.002% gave the highest sensitivity, which was 16- to 18-fold higher than deprotonated ions, and was designated as the contribution giving the strongest ionization enhancement and adduction. A number of parameters were then varied in order to optimize the method, and a limit of quantitation (LOQ) at 0.2 ng/mL was reached with an injection volume of 5 μL, a total run time of 3 min, and 0.1 mL of rat plasma. A calibration curve was plotted over the range 0.2–50 ng/mL ( R 2 = 0.9998), and the method was successfully applied to study pharmacokinetics in rat following a single oral administration of digoxin (0.05 mg/kg). Four additional steroid saponins (digitoxin, deslanoside, ginsenoside Rg1 and Rb1) were investigated to assess the impact of formic acid on the mass response of steroid saponins. Compounds with a conjugated lactonic ring in their structures such as digoxin, digitoxin and deslanoside tended to form stable formate-adduct ions more easily. The LC/MS/MS method developed here is therefore well suited for the quantification of steroid saponins that are difficult to deprotonate using other MS approaches. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
22. Two complementary liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods to study the excretion and metabolic interaction of edaravone and taurine in rats.
- Author
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Tang, Dao-quan, Zheng, Xiao-xiao, Li, Yin-jie, Bian, Ting-ting, Yu, Yan-yan, Du, Qian, Yang, Dong-zhi, and Jiang, Shui-shi
- Subjects
- *
ANTIPYRINE , *TAURINE , *LIQUID chromatography-mass spectrometry , *DRUG metabolism , *LABORATORY rats , *INTRAVENOUS injections , *DRUG interactions , *THERAPEUTICS - Abstract
In this study, two independent and complementary liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods were respectively developed and validated for the determination of edaravone or taurine in rat urine, feces and bile after intravenous administration, using 3-methyl-l- p -tolyl-5-pyrazolone and sulfanilic acid as the internal standards (IS). Edaravone was separated on an Agilent Eclipse Plus C 18 column (100 × 2.1 mm, 3.5 μm) using methanol and water (containing 5 mM ammonium formate and 0.02% formic acid) as mobile phase, while taurine was performed on a Waters Atlantis HILIC Silica column (150 × 2.1 mm, 3 μm) using acetonitrile and water (containing 5 mM ammonium formate and 0.2% formic acid) as mobile phase. The mass analysis was performed in a Triple Quadrupole mass spectrometer via multiple reaction monitoring (MRM) with negative ionization mode. The optimized mass transition ion pairs ( m/z ) for quantification were 173.1→92.2 and 187.2→106.0 for edaravone and its IS, 124.1→80.0 and 172.0→80.0 for taurine and its IS, respectively. The validated methods have been successfully applied to the excretion and metabolism interaction study of edaravone and taurine in rats after independent intravenous administration and co-administration with a single dose. The results demonstrated that there were no significant alternations on the metabolism and cumulative excretion rate of edaravone and taurine, implying that the proposed combination therapy was pharmacologically viable. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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- View/download PDF
23. Influence of Fenofibrate Treatment on Triacylglycerides, Diacylglycerides and Fatty Acids in Fructose Fed Rats.
- Author
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Kopf, Thomas, Schaefer, Hans-Ludwig, Troetzmueller, Martin, Koefeler, Harald, Broenstrup, Mark, Konovalova, Tatiana, and Schmitz, Gerd
- Subjects
- *
FENOFIBRATE , *GLYCERIDES , *FATTY acids , *FRUCTOSE , *LABORATORY rats , *MASS spectrometry , *BLOOD serum analysis , *THERAPEUTICS - Abstract
Fenofibrate (FF) lowers plasma triglycerides via PPARα activation. Here, we analyzed lipidomic changes upon FF treatment of fructose fed rats. Three groups with 6 animals each were defined as control, fructose-fed and fructose-fed/FF treated. Male Wistar Unilever Rats were subjected to 10% fructose-feeding for 20 days. On day 14, fenofibrate treatment (100 mg/kg p.o.) was initiated and maintained for 7 days. Lipid species in serum were analyzed using mass spectrometry (ESI-MS/MS; LC-FT-MS, GC-MS) on days 0, 14 and 20 in all three groups. In addition, lipid levels in liver and intestine were determined. Short-chain TAGs increased in serum and liver upon fructose-feeding, while almost all TAG-species decreased under FF treatment. Long-chain unsaturated DAG-levels (36:1, 36:2, 36:4, 38:3, 38:4, 38:5) increased upon FF treatment in rat liver and decreased in rat serum. FAs, especially short-chain FAs (12:0, 14:0, 16:0) increased during fructose-challenge. VLDL secretion increased upon fructose-feeding and together with FA-levels decreased to control levels during FF treatment. Fructose challenge of de novo fatty acid synthesis through fatty acid synthase (FAS) may enhance the release of FAs ≤16:0 chain length, a process reversed by FF-mediated PPARα-activation. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
24. UPLC-MS/MS method for determination of avicularin in rat plasma and its application to a pharmacokinetic study.
- Author
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Wei-min Zhang, Rui-fang Li, Ming Sun, Da-ming Hu, Jian-fei Qiu, and Yun-hao Yan
- Subjects
- *
HIGH performance liquid chromatography , *PHARMACOKINETICS , *LIQUID chromatography-mass spectrometry , *ACETONITRILE , *LABORATORY rats , *FORMIC acid , *DRUG-eluting stents , *DRUG administration , *THERAPEUTICS - Abstract
A rapid, sensitive and selective ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was developed and validated for the determination and pharmacokinetic investigation of avicularin in rat plasma. Sample preparation was accomplished through a simple one-step deproteinization procedure with 0.2mL of acetonitrile-methanol (9:1, v/v) to a 0.1mL plasma sample. Plasma samples were separated by UPLC on an Acquity UPLC BEH C18 column using a mobile phase consisting of acetonitrile-0.1% formic acid in water with gradient elution. The total run time was 1.60min and the elution of avicularin was at 1.20min. The detection was performed on a triple quadrupole tandem mass spectrometer in the multiple reaction-monitoring (MRM) mode using the respective transitions m/z 434.1→301.3 for avicularin and m/z 237.2→194.3 for carbamazepine (IS), respectively. The calibration curve was linear over the range of 10-3000ng/mL with a lower limit of quantitation (LLOQ) of 10ng/mL. Mean recovery of avicularin in plasma was in the range of 84.2-89.5%. Intra-day and inter-day precision were both <12%. This method was successfully applied in pharmacokinetic study after intravenous administration of 5.0mg/kg avicularin in rats. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
25. An LC-MS method for simultaneous determination of five iridoids from Zhi-zi-chi Decoction in rat brain microdialysates and tissue homogenates: Towards an in depth study for its antidepressive activity.
- Author
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Kankan Qu, Longshan Zhao, Xinyi Luo, Chenning Zhang, Pengyi Hou, Kaishun Bi, and Xiaohui Chen
- Subjects
- *
LIQUID chromatography-mass spectrometry , *IRIDOIDS , *LABORATORY rats , *MICRODIALYSIS , *ANTIDEPRESSANTS , *BLOOD-brain barrier , *BIOACTIVE compounds , *PHARMACOKINETICS , *THERAPEUTICS - Abstract
Zhi-zi-chi Decoction has been clinically utilized for the treatment of depression for more than thousand years. In order to investigate the possible bioactive components that could pass through the blood brain barrier (BBB) and the mechanism of antidepressant, a sensitive LC-MS method was developed to detect the ingredients (geniposide, scandoside methyl ester, gardenoside, deacetyl asperulosidic acid methyl ester and genipin-1-β-gentiobioside) in rat brain microdialysates and tissue homogenates samples (hippocampus, hypothalamus, premotor cortex, striatum, oblongata and cerebellum). Method development and validation are described in terms of calibration curves, extraction yield, lower limit of quantification (LLOQ), precision, accuracy, intra- and inter-day variability, which are in accordance with the requirements. Microdialysis in hippocampus demonstrated that the five iridoids possessed complete pharmacokinetic process while brain tissue homogenate method testified the distribution regularity in brain. The work clarified that the five iridoids, as antidepressant ingredients, could pass through the BBB, distribute targeted and possess complete pharmacokinetics in brain. These observations, along with the large database of rat brain microdialysates and tissue homogenates data, could enable future efforts aimed to improve our understanding of the relationship between bioactive ingredients and clinical therapy of depression. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
26. An LC-MS/MS method for the simultaneous determination of goserelin and testosterone in rat plasma for pharmacokinetic and pharmacodynamic studies.
- Author
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Shu Zhang, Jiangbin Han, Guangyi Leng, Xin Di, Chunjie Sha, Xuemei Zhang, Youxin Li, and Wanhui Liu
- Subjects
- *
LIQUID chromatography-mass spectrometry , *GOSERELIN , *THERAPEUTIC use of testosterone , *LABORATORY rats , *BLOOD plasma , *PHARMACOKINETICS , *PHARMACODYNAMICS , *ELECTROSPRAY ionization mass spectrometry , *THERAPEUTICS - Abstract
A liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) method was developed, using testosterone-d3 as a surrogate analyte, for the simultaneous quantification of goserelin and testosterone in rat plasma. According to this method, the pharmacokinetic and pharmacodynamic data were obtained from a single plasma sample aliquot. The method involved the addition of alarelin as an internal standard (IS) for goserelin and testosterone-13C3 for testosterone or testosterone-d3. The conditions for the separation of these two compounds were achieved on a ZORBAX Eclipse Plus C18 column (Agilent, 2.1×50mm, 1.8µm, Stockport, UK) in a single chromatographic run at a flow rate of 400µL/min. In order to minimize interferences of complex matrix, the extraction of plasma consisted of a protein precipitation step using methanol, followed by purification using an Oasis® HLB solid-phase extraction column. The method was validated in the concentration range of 0.01-30.0ng/mL for goserelin and 0.05-30.0ng/mL for testosterone-d3, respectively. The within- and between-run precisions were 1.7-9.2% and 2.1-6.9%, respectively. The within- and between-run accuracies were -1.8 to 5.3% and -4.9 to 4.0%, respectively. This accurate and highly specific assay provides a useful method to evaluate the pharmacokinetics and pharmacodynamics of goserelin in rats. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
27. Pharmacokinetic study of multiple active constituents from Kushen-Gancao Decoction after oral administration in rat by HPLC-MS/MS.
- Author
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Qinhui Wang, Lei Shi, Xiuling Tang, Qingwei Wang, Xueliang Dang, and Yan Zhang
- Subjects
- *
PHARMACOKINETICS , *ORAL medication , *LIQUID chromatography-mass spectrometry , *CHINESE medicine , *LABORATORY rats , *METHANOL , *THERAPEUTICS - Abstract
Kushen-Gancao Decoction (KGD) is a classic traditional Chinese herb combination in treating viral hepatitis and chronic liver diseases. This study aims to investigate the pharmacokinetic (PK) study of matrine (MT), oxymatrine (OMT), glycyrrhizic acid (GL) and glycyrrhetinic acid (GA) following oral administration of KGD in rats. A rapid, sensitive and reliable HPLC-MS/MS method was successfully developed for the simultaneous determination of MT, OMT, GL and GA in rat plasma. A Inertsil C18 analytical column was used with a gradient mobile phase system of methanol-ammonium acetate (5mM) with a flow rate of 0.5mL/min. The analysis was performed on a positive and negative ionization electrospray mass spectrometer via multi reaction monitoring (MRM). Linear calibration curves were obtained for the following concentration range: 10-5000ng/mL for MT, OMT and GL, 50-15,000ng/mL for GA in rat plasma (R²>0.99). The lower limit of quantification (LLOQ) was 5ng/mL (MT, OMT and GL) and 20ng/mL (GA). The intra- and inter-day accuracies ranged from -7.91 to 9.10% and precisions (RSD) were within 15%. The analytes were found to be stable under short-term temperature conditions, post-preparative temperature conditions, and after three freeze-thaw cycles conditions. The validated method was successfully applied to a pharmacokinetic study in rats after oral administration of KGD. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
28. Pharmacokinetics difference of multiple active constituents from decoction and maceration of Fuzi Xiexin Tang after oral administration in rat by UPLC–MS/MS.
- Author
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Zhang, Qian, Ma, Yue-ming, Wang, Zheng-tao, and Wang, Chang-hong
- Subjects
- *
PHARMACOKINETICS , *ORAL medication , *LIQUID chromatography-mass spectrometry , *LABORATORY rats , *ANTHRAQUINONES , *FLAVONES , *HERBAL medicine , *THERAPEUTICS ,THERAPEUTIC use of alkaloids - Abstract
Highlights: [•] Sixteen multiple active constituents of FXT were determined by UPLC–MS/MS in rat plasma. [•] Alkaloids, flavones and anthraquinones are the main constituents absorbed in blood. [•] Different preparation can lead to dissimilar ingredients in decoction/maceration. [•] Pharmacokinetic characterastics of compound in FXT is affected by preparation method. [•] Herb–herb interaction could be seen among traditional Chinese medicine of FXT. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
29. Simultaneous determination of five free and total flavonoids in rat plasma by ultra HPLC–MS/MS and its application to a comparative pharmacokinetic study in normal and hyperlipidemic rats.
- Author
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Wang, Xiaofan, Zhao, Xu, Gu, Liqiang, Lv, Chunxiao, He, Bosai, Liu, Zhenzhen, Hou, Pengyi, Bi, Kaishun, and Chen, Xiaohui
- Subjects
- *
HYPERLIPIDEMIA treatment , *FLAVONOIDS , *BLOOD plasma , *LABORATORY rats , *HIGH performance liquid chromatography , *PHARMACOKINETICS , *LIQUID chromatography-mass spectrometry , *THERAPEUTICS - Abstract
Highlights: [•] A uHPLC–MS/MS method was developed for the pharmacokinetic study of Shixiao San. [•] Simultaneous determination of five free and total (free and conjugated) flavonoids. The validated method was successfully applied to a comparative pharmacokinetic study. [•] The pharmacokinetic profiles in the normal and hyperlipidemic rats were elucidated. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
30. Pharmacokinetics of plantamajoside and acteoside from Plantago asiatica in rats by liquid chromatography–mass spectrometry.
- Author
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Li, Yujuan, Gan, Lin, Li, George Q., Deng, Li, Zhang, Xinshi, and Deng, Yulin
- Subjects
- *
PHARMACOKINETICS , *PLANTAGO , *LIQUID chromatography-mass spectrometry , *DRUG administration , *PHENYLPROPANOIDS , *LABORATORY rats , *THERAPEUTICS - Abstract
Highlights: [•] LC–MS method was developed for simultaneous determination of plantamajoside and acteoside in rat plasma. [•] The fully validated method was applied to pharmacokinetic study. [•] Pharmacokinetics of two analytes in rats administered with Plantago asiatica was firstly reported. [Copyright &y& Elsevier]
- Published
- 2014
- Full Text
- View/download PDF
31. Simultaneous determination of five phenolic components and paeoniflorin in rat plasma by liquid chromatography–tandem mass spectrometry and pharmacokinetic study after oral administration of Cerebralcare granule®.
- Author
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Wang, Xiang-yang, Ma, Xiao-hui, Li, Wei, Chu, Yang, Guo, Jia-hua, Li, Shu-ming, Wang, Jun-mei, Zhang, Hong-chao, Zhou, Shui-ping, and Zhu, Yong-hong
- Subjects
- *
PHENOLS , *GLUCOSIDES , *BLOOD plasma , *LABORATORY rats , *LIQUID chromatography-mass spectrometry , *PHARMACOKINETICS , *DRUG administration , *THERAPEUTICS - Abstract
Highlights: [•] LC–ESI-MS/MS utilized for PK study of five phenolic components and paeoniflorin in Cerebralcare granule®. [•] The assay simultaneously determines five phenolic components and paeoniflorin in rat plasma. [•] LLOQs of these six active components are below 5.0ng/ml. [•] This is the first pharmacokinetic study of multiple components in Cerebralcare granule®. [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
- View/download PDF
32. Bioanalytical method development and validation of milnacipran in rat plasma by LC–MS/MS detection and its application to a pharmacokinetic study.
- Author
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Kanala, Kanchanamala, T. Hwisa, Nagiat, Chandu, Babu Rao, Katakam, Prakash, Khagga, Mukkanti, Challa, B.R., and Khagga, Bhavyasri
- Subjects
CYCLOPROPANE ,PHARMACOKINETICS ,LIQUID chromatography-mass spectrometry ,ANALYTICAL chemistry ,DRUG development ,BLOOD plasma ,LABORATORY rats ,LIQUID-liquid extraction ,CHROMATOGRAPHIC analysis ,SEPARATION (Technology) ,THERAPEUTICS - Abstract
A simple, sensitive and specific liquid chromatography–tandem mass spectrometry (LC–MS/MS) method was developed for the quantification of milnacipran (MC) in rat plasma by using the liquid–liquid extraction method. Milnacipran-d10 (MCD10) was used as an internal standard (IS). Chromatographic separation was achieved on Zorbax SB-CN (4.6mm×75mm, 3.5µm) column with an isocratic mobile phase composed of 10mM ammonium acetate (pH 4.0) and methanol in the ratio of 25:75(v/v), at a flow-rate of 0.7mL/min. MC and MCD10 were detected with proton adducts at m/z 247.2→230.3 and m/z 257.2→240.4 in multiple reaction monitoring (MRM) positive mode respectively. The method was validated over a linear concentration range of 1.00–400.00ng/mL with a correlation coefficient (r
2 )≥0.9850. This method demonstrated intra- and inter-day precision within 5.40–10.85% and 4.40–8.29% and accuracy within 97.00–104.20% and 101.64–106.23%. MC was found to be stable throughout three freeze–thaw cycles, bench top and postoperative stability studies. This method was successfully applied to a pharmacokinetic study of rats through i.v. administration. [ABSTRACT FROM AUTHOR]- Published
- 2013
- Full Text
- View/download PDF
33. Structural elucidation of metabolites of lapachol in rats by liquid chromatographytandem mass spectrometry.
- Subjects
DRUG metabolism ,NAPHTHOQUINONE ,METABOLITES ,MOLECULAR structure ,DRUG development ,LIQUID chromatography-mass spectrometry ,LABORATORY rats ,TABEBUIA ,RF values (Chromatography) ,THERAPEUTICS - Published
- 2013
- Full Text
- View/download PDF
34. A fast, sensitive, and high-throughput method for the simultaneous quantitation of three ellagitannins from Euphorbiae pekinensis Radix in rat plasma by ultra- HPLC- MS/ MS.
- Author
-
Hou, Pengyi, Zeng, Yan, Ma, Bingjie, Wang, Xiaofan, Liu, Zhenzhen, Li, Lu, Qu, Kankan, Bi, Kaishun, and Chen, Xiaohui
- Subjects
- *
ELLAGITANNINS , *LABORATORY rats , *HIGH performance liquid chromatography , *LIQUID chromatography-mass spectrometry , *LIQUID-liquid extraction , *EUPHORBIA , *THERAPEUTICS - Abstract
A fast, sensitive, and high-throughput ultra- HPLC- MS/ MS method has been developed and validated for the simultaneous determination of three main active constituents of Euphorbiae pekinensis Radix in rat plasma. After addition of the internal standard, plasma samples were extracted by liquid-liquid extraction with ethyl acetate/isopropanol (1:1, v/v) and separated on a CAPCELL PAK C18 column (100 × 2.0 mm, 2 μm, Shiseido, Japan), using a gradient mobile phase system of methanol/water. The detection of the analytes was performed on a 4000 Q UHPLC- MS/ MS system with turbo ion spray source in the negative ion and multiple reaction-monitoring mode. The linear range was 1.0-1000 ng/mL for 3,3′-di- O-methyl ellagic acid-4′- O- β -d-glucopyranoside (i), 1.5-1500 ng/mL for 3,3′-di- O-methyl ellagic acid-4′- O- β -d-xylopyranoside (ii), and 5.0-5000 ng/mL for 3,3′-di- O-methyl ellagic acid (iii). The intra- and interday precision and accuracy of all the analytes were within 15%. The extraction recoveries of the three analytes and internal standard from plasma were all more than 80%. The validated method was first successfully applied to the evaluation of pharmacokinetic parameters of compounds 1, 2, and 3 in rat plasma after intragastric administration of the Euphorbiae pekinensis Radix extract. [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
- View/download PDF
35. Development of a validated LC-MS/MS method for determination of doxofylline on rat dried blood spots and urine: Application to pharmacokinetics
- Author
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Rao, R. Nageswara, Prasad, K. Guru, Naidu, Ch. Gangu, Saida, Shaik, and Agwane, Sachin B.
- Subjects
- *
XANTHINE , *LIQUID chromatography-mass spectrometry , *PHARMACOKINETICS , *TRIFLUOROACETIC acid , *ACETONITRILE , *URINALYSIS , *LABORATORY rats , *THERAPEUTICS - Abstract
Abstract: A rapid and highly sensitive liquid chromatography-tandem mass spectrometric (LC–MS/MS) method for determination of doxofylline on rat dried blood spots and urine was developed and validated. The chromatographic separation was achieved on a reverse phase C18 column (250mm×4.6mm, 5μm), using 20mM ammonium acetate (pH adjusted to 3.5 with trifluoroacetic acid) and acetonitrile (75:25 v/v) as a mobile phase at 25°C. LC–MS detection was performed with selective ion monitoring using target ions at m/z 267 and m/z 195 for doxofylline and caffeine used as internal standard respectively. The calibration curve showed a good linearity in the concentration range of 1–5000ng/mL. The effect of hematocrit on extraction of doxofylline from DBS was evaluated. The mean recoveries of doxofylline from DBS and urine were 93.46 and 89.86% respectively. The intra and inter-day precisions were less than 4.28% in DBS as well as urine. The limit of detection and quantification were 0.24 and 0.84ng/mL in DBS and 0.28 and 1.00ng/mL in urine samples respectively. The method was validated as per ICH guidelines and successfully applied to a pharmacokinetic study of doxofylline in rats. [Copyright &y& Elsevier]
- Published
- 2013
- Full Text
- View/download PDF
36. Development and validation of a simple and sensitive method for quantification of levodopa and carbidopa in rat and monkey plasma using derivatization and UPLC–MS/MS.
- Author
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Junnotula, Venkatraman and Licea-Perez, Hermes
- Subjects
- *
DOPA , *HYDRAZINES , *BLOOD plasma , *LIQUID chromatography-mass spectrometry , *DERIVATIZATION , *LABORATORY rats , *LABORATORY monkeys , *THERAPEUTICS - Abstract
Highlights: [•] Derivatization of levodopa and carbidopa with fluorescamine. [•] Derivatization improved chromatographic retention and sensitivity. [•] The method was validated over the concentration range of 5/3–5000/3000ng/mL for levodopa/carbidopa. [•] This method was successfully employed in the analysis of rat and monkey plasma study samples. [Copyright &y& Elsevier]
- Published
- 2013
- Full Text
- View/download PDF
37. Development of an LC–MS method for determination of three active constituents of Shuang-huang-lian injection in rat plasma and its application to the drug interaction study of Shuang-huang-lian freeze-dried powder combined with levofloxacin injection
- Author
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Ye, Jing, Song, Xiaowei, Liu, Zhihong, Zhao, Xu, Geng, Lulu, Bi, Kaishun, and Chen, Xiaohui
- Subjects
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LIQUID chromatography-mass spectrometry , *BLOOD plasma , *DRUG interactions , *LABORATORY rats , *FREEZE-drying , *FLUOROQUINOLONES , *SEPARATION (Technology) , *THERAPEUTICS - Abstract
Abstract: A sensitive and specific high performance liquid chromatography coupled with mass spectrometric (LC–MS) method was developed and validated for the simultaneous determination of three main active constituents of Shuang-huang-lian injection with and without the combination use of levofloxacin injection in rat plasma. After addition of the internal standard rutin, plasma samples were protein precipitated with acetonitrile, the chromatographic separation was achieved on a Kromasil C18 column (250mm×4.6mm, 5μm), using a gradient mobile phase system of acetonitrile–water containing 0.05% formic acid. The analytes were detected without interference in the selected ion monitoring (SIM) mode with positive electrospray ionization. The linear range was 0.04–20μg/mL for chlorogenic acid, 0.8–400μg/mL for baicalin and 0.01–5.0μg/mL for phillyrin, respectively. The accuracy (relative error, R.E.%) were between −2.7 and 3.4%, while the intra-day and inter-day precisions were less than 9.2 and 9.6% for the three analytes, respectively. This method was successfully applied to the drug interaction study of Shuang-huang-lian freeze-dried powder combined with levofloxacin injection after intravenous administration to rats. The results indicated that there were obvious differences in the pharmacokinetic behaviors after combination compared with only administration of Shuang-huang-lian injection. [Copyright &y& Elsevier]
- Published
- 2012
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