scholarly journals Simultaneous Quantification and Pharmacokinetic Study of Five Homologs of Dalbavancin in Rat Plasma Using UHPLC-MS/MS

Molecules ◽  
2020 ◽  
Vol 25 (18) ◽  
pp. 4100
Author(s):  
Difeng Zhu ◽  
Li Ping ◽  
Yawen Hong ◽  
Jiale Shen ◽  
Qinjie Weng ◽  
...  
Keyword(s):  
High Performance ◽  
Multiple Reaction Monitoring ◽  
Gradient Elution ◽  
Rat Plasma ◽  
Pharmacokinetic Analysis ◽  
Pharmacokinetic Studies ◽  
Quadrupole Mass ◽  
Triple Quadrupole Mass Spectrometer ◽  
Liquid Chromatography Tandem Mass ◽  
Multiple Reaction Monitoring Mode

Dalbavancin is a novel semisynthetic glycopeptide antibiotic that comprises multiple homologs and isomers of similar polarities. However, pharmacokinetic studies have only analyzed the primary components of dalbavancin, namely B0 and B1. In this study, an ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed to simultaneously determinate and investigate the five homologous components of dalbavancin, namely, A0, A1, B0, B1, and B2, in rat plasma. In this method, methanol was used to precipitate plasma, and a triple-bonded alkyl chromatographic column was used for molecule separation, using 0.1% formic acid-acetonitrile as the mobile phase for gradient elution. Targeted homologs were analyzed by a triple quadrupole mass spectrometer using positive electrospray ionization in multiple reaction monitoring mode. The linearity range was 50–2500 ng/mL with a high correlation coefficient (r2 > 0.998). This method was successfully applied in the pharmacokinetic analysis of dalbavancin hydrochloride to investigate dalbavancin components in rats.

Simultaneous Determination of Three Coumarins in Rat Plasma by HPLC-MS/MS for Pharmacokinetic Studies Following Oral Administration of Chimonanthi Radix Extract

2020 ◽  
Vol 58 (10) ◽  
pp. 922-928
Author(s):  
Jing Zhang ◽  
Quan Wen ◽  
Meng-ying Zhou ◽  
Chen-cong Zhong ◽  
Yulin Feng ◽  
...  
Keyword(s):  
Oral Administration ◽  
High Performance ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Gradient Elution ◽  
Rat Plasma ◽  
Pharmacokinetic Studies ◽  
Bioactive Constituents ◽  
Liquid Chromatography Tandem Mass ◽  
Multiple Reaction Monitoring Mode

Abstract Chimonanthi Radix (CR) is widely used in the treatment of influenza in China. Extensive studies revealed that the major bioactive constituents of CR were coumarins. However, pharmacokinetic study of coumarins in CR has not been fully studied. The purpose of this study was to establish a convenient and effective high-performance liquid chromatography–tandem mass spectrometry method that was used to simultaneously determine scopoletin, scopolin and isofraxidin in rat plasma after oral administration of CR extract using xanthotoxin as the internal standard. The chromatographic separation was carried out on a COSMOCORE C18 column (100 × 2 mm, 2.6 μm), using gradient elution with the mobile phase consisting of 0.1% formic acid (A) and acetonitrile (B). Three coumarins and IS were quantified by positive ion electrospray ionization in multiple reaction monitoring mode. The method was fully validated in terms of specificity, accuracy, precision (intra- and inter-day), matrix effect, recovery as well as the stability of the analytes under various conditions. The results could provide further research foundation for anti-influenza mechanism of three coumarins in CR.

scholarly journals An LC-MS/MS Method for Simultaneous Determination of the Toxic and Active Components of Cortex Periplocae in Rat Plasma and Application to a Pharmacokinetic Study

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Zhen Li ◽  
Yang Li ◽  
Jin Li ◽  
Rui Liu ◽  
Jia Hao ◽  
...  
Keyword(s):  
Oral Administration ◽  
Multiple Reaction Monitoring ◽  
Gradient Elution ◽  
Rat Plasma ◽  
Pharmacokinetic Studies ◽  
Simple Liquid ◽  
Active Components ◽  
Limit Of Quantification ◽  
Liquid Chromatography Tandem Mass

A sensitive and simple liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated to simultaneously determine the toxic and other active components including isovanillin, scopoletin, periplocin, periplogenin, and periplocymarin after oral administration of cortex periplocae extract to rats. Plasma samples were prepared by protein precipitation with methanol. All compounds were separated on a C18 column with gradient elution using acetonitrile and formic acid aqueous solution (0.1%, v/v) as the mobile phase at a flow rate of 0.3 mL/min. The detection of all compounds was accomplished by multiple-reaction monitoring (MRM) in the positive electrospray ionization mode. The LC-MS/MS method exhibited good linearity for five analytes. The lower limit of quantification (LLOQ) was 0.48 ng/mL for scopoletin, periplogenin, and periplocymarin; 2.4 ng/mL for isovanillin and periplocin. The extraction recoveries of all compounds were more than 90% and the RSDs were below 10%. It was found that the absorption of scopoletin and periplocin was rapid in vivo after oral administration of cortex periplocae extract. Furthermore, periplocymarin possessed abundant plasma exposure. The results demonstrated that the validated method was efficiently applied for the pharmacokinetic studies of isovanillin, scopoletin, periplocin, periplogenin, and periplocymarin after oral administration of cortex periplocae extract.

scholarly journals Simultaneous Quantification and Pharmacokinetic Study of Nine Bioactive Components of Orthosiphon stamineus Benth. Extract in Rat Plasma by UHPLC-MS/MS

Molecules ◽  
2019 ◽  
Vol 24 (17) ◽  
pp. 3057 ◽  
Author(s):  
Guo ◽  
Li ◽  
Gu ◽  
Zhu ◽  
Su ◽  
...  
Keyword(s):  
High Performance ◽  
Multiple Reaction Monitoring ◽  
Rat Plasma ◽  
Negative Ion ◽  
Pharmacokinetic Analysis ◽  
Bioactive Components ◽  
Triple Quadrupole Mass Spectrometer ◽  
Salvianolic Acid ◽  
Orthosiphon Stamineus ◽  
Simultaneous Quantification

Orthosiphon stamineus Benth. (OS) is a traditional folk medicine for the treatment of kidney stones and other urinary tract diseases. In this study, a rapid and sensitive Ultra high-performance liquid chromatography (UHPLC)-MS/MS approach was established and validated for the simultaneous quantification of nine bioactive components in rat plasma. The nine components from OS extract detected in rat plasma were danshensu, protocatechuic acid, caffeic acid, rosmarinic acid, salvianolic acid A, salvianolic acid B, cichoric acid, sinensetin and eupatorin. After liquid-liquid extraction with ethyl acetate, the plasma samples were subjected to a triple quadrupole mass spectrometer employing electrospray ionization (ESI) technique and operating in multiple reaction monitoring (MRM) with both positive and negative ion modes. The standard curves showed good linear regression (r > 0.9915) over the concentration range for the nine analytes. The inter-day and intra-day precision and accuracy were found to be within 15% of the nominal concentration. The recovery and stability of nine compounds were all demonstrated to be within acceptable limits. The approach was successfully applied to investigate the pharmacokinetic analysis of the nine bioactive components after oral administration of OS extract in rats.

scholarly journals Simultaneous determination of calycosin, prim-O-glucosylcimifugin, and paeoniflorin in rat plasma by HPLC-MS/MS: application in the pharmacokinetic analysis of HQCF

2020 ◽  
Vol 48 (11) ◽  
pp. 030006052097290
Author(s):  
Yulong Gu ◽  
Xianglan Piao ◽  
Dan Zhu
Keyword(s):  
Formic Acid ◽  
High Performance ◽  
Internal Standard ◽  
Gradient Elution ◽  
Rat Plasma ◽  
Selected Reaction Monitoring ◽  
Pharmacokinetic Analysis ◽  
Ionization Source ◽  
Liquid Chromatography Tandem Mass

Objective This study aimed to develop and validate a high-performance liquid chromatography–tandem mass spectrometry method to simultaneously determine three bioactive components of the Huangqi Chifeng decoction (HQCF) in rat plasma. Methods Taxol was used as an internal standard in the developed method. Chromatographic separation was performed on a C18 column using a gradient elution with 0.1% formic acid in acetonitrile (v/v) and 0.1% formic acid in water (v/v) as the mobile phases at a flow rate of 0.4 mL·minute−1. All compounds were monitored via selected reaction monitoring with an electrospray ionization source. Results The lower limits of quantification of paeoniflorin, calycosin, and prim- O-glucosylcimifugin were 15.0, 0.75, and 0.75 ng·mL−1, respectively. The calibration curves indicated optimal linearity ( r > 0.99) across the concentration ranges. The specificity, precision, accuracy, recovery, matrix effect, and stability of the method were validated. This method was successfully applied in a pharmacokinetics study of the three compounds in rat plasma. Conclusion The pharmacokinetics results provide insights into the mechanisms of HQCF in vivo and its future clinical application.

scholarly journals Multiresidue Analysis of Pesticides in Soil by High-Performance Liquid Chromatography with Tandem Mass Spectrometry

2009 ◽  
Vol 92 (5) ◽  
pp. 1566-1575 ◽  
Author(s):  
José Fenoll ◽  
Pilar Hellín ◽  
Carmen M Martnez ◽  
Pilar Flores
Keyword(s):  
High Performance ◽  
Single Phase ◽  
Multiple Reaction Monitoring ◽  
Soil Samples ◽  
Reaction Monitoring ◽  
Quadrupole Mass ◽  
Triple Quadrupole Mass Spectrometer ◽  
Multiresidue Analysis ◽  
Multiple Reaction Monitoring Mode

Abstract An analytical multiresidue method using HPLC/MS/MS with a triple-quadrupole mass spectrometer in the multiple reaction monitoring mode for the simultaneous determination of 54 pesticides in soil has been developed. The procedure involved initial single-phase extraction of soil sample with acetonitrile by sonication, followed by liquidliquid partitioning after addition of NaCl. The average recovery by the HPLC/MS/MS method obtained for these compounds varied from 63.2 to 113.8, with an RSD between 1.9 and 7.1. The method gave good linearity over the assay range of 10500 g/L (except famoxadone, 501000 g/L); the LOD and LOQ for the pesticides varied from 0.02 to 13.2 and from 0.1 to 43.9 g/kg, respectively. The proposed method was used to determine pesticide levels in soil samples from two experimental vineyards and two tomato greenhouses.

scholarly journals Development and Validation of a Sensitive, Specific and Reproducible UPLC-MS/MS Method for the Quantification of OJT007, A Novel Anti-Leishmanial Agent: Application to a Pharmacokinetic Study

2021 ◽  
Vol 18 (9) ◽  
pp. 4624
Author(s):  
Maria Rincon Nigro ◽  
Jing Ma ◽  
Ololade Tosin Awosemo ◽  
Huan Xie ◽  
Omonike Arike Olaleye ◽  
...  
Keyword(s):  
Formic Acid ◽  
High Performance ◽  
Leishmania Major ◽  
Internal Standard ◽  
Gradient Elution ◽  
Rat Plasma ◽  
The Matrix ◽  
Liquid Chromatography Tandem Mass ◽  
Positive Mode ◽  
Acquity Uplc

OJT007 is a methionine aminopeptidase 1 (MetAP1) inhibitor with potent anti-proliferative effects against Leishmania Major. In order to study its pharmacokinetics as a part of the drug development process, a sensitive, specific, and reproducible ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated. Voriconazole was used as the internal standard to generate standard curves ranging from 5 to 1000 ng/mL. The separation was achieved using a UPLC system equipped with an Acquity UPLC BEH C18 column (2.1 × 50 mm, 1.7 μm) with 0.1% formic acid in acetonitrile and 0.1% formic acid in water as the mobile phase under gradient elution at a flow rate of 0.4 mL/min. The mass analysis was performed with a 4000 QTRAP® mass spectrometer using multiple-ion reaction monitoring (MRM) in the positive mode, with the transition of m/z 325 → m/z 205 for OJT007 and m/z 350 → m/z 101 for voriconazole. The intra- and inter-day precision and accuracy were within ±15%. The mean extraction recovery and the matrix effect were 95.1% and 7.96%, respectively, suggesting no significant matrix interfering with the quantification of the drug in rat plasma. This study was successfully used for the pharmacokinetic evaluation of OJT007 using the rat as an animal model.

scholarly journals UHPLC-QQQ-MS/MS assay for quantification of dianthrones as potential toxic markers of Polygonum multiflorum Thunb: Application to the standardization of TCMs with endogenous toxicity

2021 ◽  
Author(s):  
Jian-Bo Yang ◽  
Yun-Fei Song ◽  
Yue Liu ◽  
Hui-Yu Gao ◽  
Qi Wang ◽  
...  
Keyword(s):  
High Performance ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Triple Quadrupole ◽  
Quadrupole Mass ◽  
Polygonum Multiflorum ◽  
Triple Quadrupole Mass Spectrometer ◽  
Benefit Risk Assessment ◽  
Heparg Cells

Abstract Background: The raw and processed roots of Polygonum multiflorum Thunb (PM) are commonly used in clinical practice to treat diverse diseases; however, the reports of hepatotoxicity induced by Polygoni Multiflori Radix (PMR) and Polygoni Multiflori Radix Praeparata (PMRP) have emerged worldwide. Thus, it is necessary for researcher to explore the methods to improve its quality standards and further ensure its quality and treatment effect.Methods: In the present study, an ultra-high-performance liquid chromatography coupled with triple quadrupole mass spectrometry (UHPLC-QQQ- MS/MS) method has been optimized and validated for the determination of dianthrones in PMR and PMRP, using bianthronyl as the internal standard. Chromatographic separation with a gradient mobile phase (A: acetonitrile and B: water containing 0.1% formic acid (v/v)) at a flow rate of 0.25 mL/min was achieved on a Waters Acquilty UPLC BEH b) C18 column (2.1 mm × 50 mm, 1.7 µm). A triple quadrupole mass spectrometer (TQMS) was operated in negative ionization mode with multiple reaction monitoring for the quantitative analysis of six dianthrones. Meanwhile, compounds 5 and 6 were further evaluated for cytotoxicity of HepaRG cells by CCK8 assay.Results: The UHPLC-QQQ-MS/MS method was first developed to simultaneous determination of six dianthrones in PMR and PMRP, namely polygonumnolides C1–C4 (1–4), trans-emodin dianthrones (5), and cis-emodin dianthrones (6). The contents of 1~6 in 90 batches of PMR were in the range of 0.027-19.04, 0.022-13.86, 0.073 -15.53, 0.034 -23.35, 0.38-83.67 and 0.29 -67.00 µg/g, respectively. The contents of 1~6 in 86 batches of commercial PMRP were in the range of 0.020-13.03, 0.051-8.94, 0.022-7.23, 0.030 -12.75, 0.098-28.54 and 0.14-27.79 µg/g, respectively. The six dianthrones were almost completely gone after reasonable processing for 24 h. Meanwhile, compounds 5 and 6 showed the inhibitory activity against HepaRG cells with the IC50 values of 10.98 and 15.45 μM, respectively. Furthermore, a systematic five-step strategy to realize the standardization of TCMs with endogenous toxicity is proposed for the first time, involving the establishment of determination methods, determination of the toxic markers, the standardization of processing method, the development of limit standards and benefit-risk assessment.Conclusion: The results of cytotoxicity evaluation of dianthrone indicated that trans-emodin dianthrones (5) and cis-emodin dianthrones (6) could be selected as the toxic markers of PMRP. Taking PMR and PMRP for example, we hope this study provided insight into the standardization and internationalization of endogenous toxic TCMs, with the main purpose of improving public health by scientifically using TCMs to treat diverse complex diseases in future.

scholarly journals Pharmacokinetics of isocorynoxeine in rat plasma after intraperitoneal administration by UPLC–MS/MS

2020 ◽  
Vol 32 (4) ◽  
pp. 260-263
Author(s):  
Haichao Zhan ◽  
Zhen Wei ◽  
Ke Ren ◽  
Shuhua Tong ◽  
Xianqin Wang ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Tandem Mass Spectrometry ◽  
Multiple Reaction Monitoring ◽  
Intraperitoneal Administration ◽  
Gradient Elution ◽  
Ultra Performance Liquid Chromatography ◽  
Rat Plasma ◽  
Tandem Mass ◽  
Relative Standard ◽  
Liquid Chromatography Tandem Mass

Isocorynoxeine is one of the main alkaloids in Chinese medicinal herbs, and has pharmacological activities such as antihypertensive, sedative, anticonvulsant, and neuronal protection. It is an effective component of Uncaria for the treatment of hypertension. In this study, we used a fast and sensitive ultra-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) to detect isocorynoxeine in rat plasma and investigated its pharmacokinetics in rats. Six rats were given isocorynoxeine (15 mg/kg) by intraperitoneal (i.p.) administration. Blood (100 μL) was withdrawn from the caudal vein at 5 and 30 min and 1, 2, 4, 6, 8, 12, and 24 h after administration. Chromatographic separation was achieved using a UPLC BEH C18 column using a mobile phase of acetonitrile–0.1% formic acid with gradient elution. Electrospray ionization (ESI) tandem mass spectrometry in the multiple reaction monitoring (MRM) mode with positive ionization was applied. Intra-day and inter-day precisions (relative standard deviation, %RSD) of isocorynoxeine in rat plasma were lower than 12%. The method was successfully applied in the pharmacokinetics of isocorynoxeine in rats after intraperitoneal administration. The t1/2 of isocorynoxeine is 4.9 ± 2.1 h, which indicates quick elimination.

scholarly journals Determination of Matrine in Rat Plasma after Oral Administration of Novel Korean Herbal Medicine KIOM-MA128 and Application of PK

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Hyun-moon Back ◽  
Byungjeong Song ◽  
Jung-woo Chae ◽  
Hwi-yeol Yun ◽  
Jin Yeul Ma ◽  
...  
Keyword(s):  
Herbal Medicine ◽  
Oral Administration ◽  
High Performance ◽  
Rat Plasma ◽  
Pharmacokinetic Studies ◽  
Chemical Marker ◽  
Chromatography Tandem Mass Spectrometry ◽  
Accuracy And Precision ◽  
Liquid Chromatography Tandem Mass

KIOM-MA128 is a novel Korean herbal medicine with antiatopic, anti-inflammatory, and antiasthmatic effects. Matrine is thought to be a potential chemical marker of KIOM-MA128, but pharmacokinetic studies on KIOM-MA128 had not been performed. This study describes a simple and rapid method using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) to determine the concentration of matrine in rats plasma after administration of KIOM-MA128. The isocratic mobile phase consisted of methanol and distilled water, and the flow rate was 0.15 mL/min. The accuracy and precision of the assay, as well as stability tests, were performed in accordance with FDA regulations for the validation of bioanalytical methods. The half-life andTmaxof matrine after administration of KIOM-MA128 were 4.29 ± 2.20 h and 1.8 ± 1.23 h, respectively.CmaxandAUCinfof matrine after administration of KIOM-MA128 at 4 g/kg and 8 g/kg were 595.10 ± 182.91 ng/mL, 5336.77 ± 1503.84 ng/mL·h and 850.46 ± 120 ng/mL, 9583.10 ± 888.92 ng/mL·h, respectively. The validated method was successfully applied to a pharmacokinetic study in rats after oral administration of KIOM-MA128.

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