scholarly journals Development of UHPLC-MS/MS Method for Indirubin-3′-Oxime Derivative as a Novel FLT3 Inhibitor and Pharmacokinetic Study in Rats

Molecules ◽  
2020 ◽  
Vol 25 (9) ◽  
pp. 2039
Author(s):  
Na Yoon Kim ◽  
Yong-Chul Kim ◽  
Yoon Gyoon Kim
Keyword(s):  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Rat Plasma ◽  
Reaction Monitoring ◽  
Spectrometry Method ◽  
Limit Of Quantification ◽  
Flt3 Inhibitor ◽  
Pharmacokinetic Properties ◽  
Safety Guidelines ◽  
The U.S

This study aimed to develop and validate a sensitive liquid chromatography-coupled tandem mass spectrometry method for the quantification of LDD-2614, an indirubin derivative and novel FLT3 inhibitor, in rat plasma. In addition, the developed analytical method was applied to observe the pharmacokinetic properties of LDD-2614. Chromatographic separation was achieved on a Luna omega C18 column using a mixture of water and acetonitrile, both containing 0.1% formic acid. Quantitation was performed using positive electrospray ionization in a multiple reaction monitoring (MRM) mode. The MRM transitions were optimized as m/z 426.2→113.1 for LDD-2614 and m/z 390.2→113.1 for LDD-2633 (internal standard), and the lower limit of quantification (LLOQ) for LDD-2614 was determined as 0.1 ng/mL. Including the LLOQ, the nine-point calibration curve was linear with a correlation coefficient greater than 0.9991. Inter- and intraday accuracies (RE) ranged from −3.19% to 8.72%, and the precision was within 9.02%. All validation results (accuracy, precision, matrix effect, recovery, stability, and dilution integrity) met the acceptance criteria of the U.S. Food and Drug Administration and the Korea Ministry of Food and Drug Safety guidelines. The proposed method was validated and demonstrated to be suitable for the quantification of LDD-2614 for pharmacokinetics studies.

Determination of Shanzhiside Methylester in Rat Plasma by Uplc-Ms/Ms and its Application to a Pharmacokinetic Study

2020 ◽  
Vol 16 (7) ◽  
pp. 960-966
Author(s):  
Qinghua Weng ◽  
Yichuan Chen ◽  
Zuoquan Zhong ◽  
Qianqian Wang ◽  
Lianguo Chen ◽  
...  
Keyword(s):  
Mobile Phase ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Gradient Elution ◽  
Rat Plasma ◽  
Precipitation Method ◽  
Reaction Monitoring ◽  
Limit Of Quantification ◽  
Pharmacokinetics In Rats

Introduction: In this study, we used UPLC-MS/MS to detect shanzhiside methylester in rat plasma, and investigated its pharmacokinetics in rats. Materials and Methods: Diazepam was utilized as an internal standard (IS), and acetonitrile precipitation method was used to process the plasma samples. Chromatographic separation was achieved using a UPLC BEH C18 column using mobile phase of methanol-0.1 % formic acid with gradient elution. Electrospray ionization (ESI) tandem mass spectrometry in multiple reaction monitoring (MRM) mode with positive ionization was applied. Results: The results indicated that within the range of 5-4000 ng/mL, linearity of shanzhiside methylester in rat plasma was acceptable (r>0.995), and the lower limit of quantification (LLOQ) was 5 ng/mL. Intra-day and inter-day precision RSD of shanzhiside methylester in rat plasma were lower than 14%. Accuracy range was between 87.3 % and 109.1 %, and matrix effect was between 99.2% and 106.3%. Conclusion: The method was successfully applied in the pharmacokinetics of shanzhiside methylester in rats after intravenous administration.

scholarly journals Determination of sarecycline by UPLC-MS/MS and its application to pharmacokinetic study in rats

2020 ◽  
Author(s):  
Yonghui Shen ◽  
Deru Meng ◽  
Feifei Chen ◽  
Hui Jiang ◽  
Liming Hu ◽  
...  
Keyword(s):  
Pharmacokinetic Study ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Gradient Elution ◽  
Rat Plasma ◽  
Chronic Inflammatory Disease ◽  
Linear Calibration ◽  
Limit Of Quantification ◽  
Acquity Uplc ◽  
Intravenous And Oral Administration

AbstractSarecycline is a narrow-spectrum antibiotic for the treatment of acne, which is a chronic inflammatory disease of the hair follicle sebaceous glands. In the study, UPLC-MS/MS was used to establish a rapid and accurate analytical method. The sarecycline was determined with poziotinib as internal standard (IS) in rat plasma. An ACQUITY UPLC HSS T3 column (2.1 × 100 mm, 1.8 μm) could performe chromatographic separation with the mobile phase (methanol: water of 0.1% formic acid) with gradient elution. The ions of target fragment were m/z 488.19→410.14 for sarecycline and m/z 492.06→354.55 for poziotinib, which could quantify the electrospray ionization of positive multiple reaction monitoring (MRM) mode. The linear calibration curve of the concentration range was 1–1,000 ng/mL for sarecycline with a lower limit of quantification (LLOQ) of 1 ng/mL. The mean recovery was between 82.46 and 95.85% for sarecycline and poziotinib in rat plasma. RSD for precision of inter-day and intra-day were between 3.24 and 13.36%, and the accuracy ranged from 105.26 to 109.75%. The developed and validated method was perfectly used in the pharmacokinetic study and bioavailability of sarecycline after intravenous and oral administration in rats.

scholarly journals Development and Validation of a Sensitive UHPLC-MS/MS Method for the Measurement of Gardneramine in Rat Plasma and Tissues and its Application to Pharmacokinetics and Tissue Distribution Study

Molecules ◽  
2019 ◽  
Vol 24 (21) ◽  
pp. 3953 ◽  
Author(s):  
Zhao ◽  
Tan ◽  
Chen ◽  
Sun ◽  
Wang ◽  
...  
Keyword(s):  
Multiple Reaction Monitoring ◽  
Indole Alkaloid ◽  
Internal Standard ◽  
Gradient Elution ◽  
Rat Plasma ◽  
Limit Of Quantification ◽  
Tissue Samples ◽  
Distribution Study

As a novel monoterpenoid indole alkaloid, gardneramine has been confirmed to possess excellent nervous depressive effects. However, there have been no reports about the measurement of gardneramine in vitro and in vivo. The motivation of this study was to establish and validate a specific, sensitive, and robust analytical method based on UHPLC-MS/MS for quantification of gardneramine in rat plasma and various tissues after intravenous administration. The analyte was extracted from plasma and tissue samples by protein precipitation with methanol using theophylline as an internal standard (I.S.). The analytes were separated on an Agilent ZORBAX Eclipse Plus C18 column using a gradient elution of acetonitrile and 0.1% formic acid in water at a flow rate of 0.3 mL/min. Gardneramine and I.S. were detected and quantified using positive electrospray ionization in multiple reaction monitoring (MRM) mode with transitions of m/z 413.1→217.9 for gardneramine and m/z 181.2→124.1 for I.S.. Perfect linearity range was 1–2000 ng/mL with a correlation coefficient (r2) of ≥0.990. The lower limit of quantification (LLOQ) of 1.0 ng/mL was adequate for application to different preclinical studies. The method was successfully applied for determination of gardneramine in bio-samples.

scholarly journals Simultaneous determination and pharmacokinetics studies of five isoflavones in rat plasma by UHPLC-MS/MS after oral administration of Radix Astragali extract

2021 ◽  
Author(s):  
Jianwei Han ◽  
Wenbo Zhu ◽  
Ling Yu ◽  
Yajun Chen ◽  
Gaosong Wu ◽  
...  
Keyword(s):  
Oral Administration ◽  
High Performance ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Rat Plasma ◽  
Tandem Mass ◽  
Radix Astragali ◽  
Limit Of Quantification ◽  
Liquid Chromatography Tandem Mass ◽  
Mass Spectrometery

AbstractA rapid, sensitive and convenient method based on ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) was developed and validated for the simultaneous quantification of calycosin-7-O-β-d-glucoside (CCSG), ononin, calycosin, (6aR,11aR)-9,10-dimethoxypterocarpan-3-O-β-d-glucopyanoside (DPPG), and 7,2′-dihydroxy-3′,4′-dimethoxyisoflavan-7-O-β-d-glucopyanoside (DIFG) in rat plasma after oral administration of the methanol extraction from Radix Astragali. Theophylline played the role of internal standard (IS). Preparation of plasma samples by liquid-liquid extraction method with ethyl acetate after precipitation of protein with methanol. The analytes were detected with a triple quadrupole tandem mass spectrometery (MS) in multiple reaction monitoring (MRM) mode and a positive ion electrospray ionization (ESI). The method was validated with the concentration ranges of 1.96–62.69 ng/mL for CCSG, 1.70–54.5 ng/mL for ononin, 1.85–59.06 ng/mL for calycosin, 2.14–137.24 ng/mL for DPPG and1.96–125.25 ng/mL for DIFG, respectively. The method had the lower limit of quantification (LLOQ) with 0.49, 0.21, 0.92, 1.07, and 0.98 ng/mL for CCSG, ononin, calycosin, DPPG and DIFG respectively, and the precision less than 10%. The RSD of the accuracy was in the range of −4.35–8.91%. The results may be helpful to provide more accurate references to clinical application of this herb.

scholarly journals Simultaneous Determination of Ropivacaine and 3-Hydroxy Ropivacaine in Cerebrospinal Fluid by UPLC-MS/MS

2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Siyuan Chen ◽  
Jianshe Ma ◽  
Xianqin Wang ◽  
Quan Zhou
Keyword(s):  
Cerebrospinal Fluid ◽  
Extraction Efficiency ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Reaction Monitoring ◽  
Limit Of Quantification ◽  
Liquid Liquid Extraction ◽  
The Matrix ◽  
Interday Precision

In this paper, a UPLC-MS/MS method was developed for the determination of ropivacaine and its metabolite 3-hydroxy ropivacaine in cerebrospinal fluid. The cerebrospinal fluid was processed by ethyl acetate liquid-liquid extraction. The multiple reaction monitoring (MRM) mode was used for quantitative analysis by monitoring the transitions of m/z 275.3 → 126.2 for ropivacaine, m/z 291.0 → 126.0 for 3-hydroxy ropivacaine, and m/z 290.2 → 198.2 for the internal standard. Standard curves for ropivacaine and 3-hydroxy ropivacaine in cerebrospinal fluid were conducted over the concentration range of 0.2–2000 ng/mL, demonstrating excellent linearity, and the lower limit of quantification was 0.2 ng/mL. The intraday precision of ropivacaine and 3-hydroxy ropivacaine was less than 11%, while the interday precision was less than 7%. The accuracy ranged between 87% and 107%, the average extraction efficiency was higher than 79%, and the matrix effect was between 89% and 98%. The developed method was then applied to a case of suspected poisoning of ropivacaine.

scholarly journals Pharmacokinetics of Lusutrombopag, a Novel Thrombopoietin Receptor Agonist, in Rats by UPLC-MS/MS

2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Bo Wang ◽  
Feifei Chen ◽  
Quan Zhou ◽  
Yunfang Zhou ◽  
Deru Meng ◽  
...  
Keyword(s):  
Receptor Agonist ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Gradient Elution ◽  
Rat Plasma ◽  
Linear Calibration ◽  
Limit Of Quantification ◽  
Mass Spectrometric Measurement ◽  
Thrombopoietin Receptor ◽  
Positive Ion

Lusutrombopag is a second oral thrombopoietin (TPO) receptor agonist that selectively acts on human TPO receptors. In the study, UPLC-MS/MS was used to establish a selective and sensitive method to determine lusutrombopag with poziotinib as IS (internal standard) in rat plasma. Samples were prepared by precipitating protein with acetonitrile as a precipitant. Separation of lusutrombopag and poziotinib was performed on a CORTECS UPLC C18 column (2.1 ∗ 50 mm, 1.6 μm). The mobile phase (acetonitrile and water containing 0.1% formic acid) with gradient elution was set at a flow rate of 0.4 ml/min. The mass spectrometric measurement was conducted under positive ion mode using multiple reaction monitoring (MRM) of m/z 592.97 ⟶ 491.02 for lusutrombopag and m/z for poziotinib (IS) 492.06 ⟶ 354.55. The linear calibration curve of the concentration range was 2–2000 ng/ml for lusutrombopag, with a lower limit of quantification (LLOQ) of 2 ng/ml. RSD of interday and intraday precision were both no more than 9.66% with the accuracy ranging from 105.82% to 108.27%. The extraction recovery of lusutrombopag was between 82.15% and 90.34%. The developed and validated method was perfectly used in the pharmacokinetic study of lusutrombopag after oral administration in rats.

scholarly journals A Validated LC-MS/MS Method for Simultaneous Determination of Six Aconitum Alkaloids and Seven Ginsenosides in Rat Plasma and Application to Pharmacokinetics of Shen-Fu Prescription

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Huizi Ouyang ◽  
Fang Liu ◽  
Zhidan Tang ◽  
Xiaopeng Chen ◽  
Fang Bo ◽  
...  
Keyword(s):  
Oral Administration ◽  
Simultaneous Determination ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Rat Plasma ◽  
Reaction Monitoring ◽  
Mass System ◽  
Acid Aqueous Solution ◽  
Interday Precision

A sensitive and reliable LC-MS/MS method has been developed and validated for simultaneous determination of six Aconitum alkaloids (aconitine, hypaconitine, mesaconitine, benzoylaconitine, benzoylhypacoitine, and benzoylmesaconine) and seven ginsenosides (Rb1, Rb2, Rc, Rd, Re, Rf, and Rg1) in rat plasma after oral administration of Shen-Fu prescription. Psoralen was selected as internal standard (IS). Protein precipitation with methanol was used in sample preparation. The chromatographic separation was achieved on a CORTECS™ C18 column with 0.1% formic acid aqueous solution and acetonitrile as mobile phase. The flow rate was 0.3 mL/min. The detection was performed on a tandem mass system with an electrospray ionization (ESI) source in the positive ionization and multiple-reaction monitoring (MRM) mode. The calibration curves of six Aconitum alkaloids and seven ginsenosides were linear over the range of 0.1-50 and 1-500 ng/mL, respectively. The extraction recoveries of the analytes in plasma samples ranged from 64.2 to 94.1%. Meanwhile, the intra- and interday precision of the analytes were less than 14.3%, and the accuracy was in the range of −14.2% to 9.8%. The developed method was successfully applied to the pharmacokinetics of six Aconitum alkaloids and seven ginsenosides in rat plasma after oral administration of Shen-Fu prescription.

Validation of an UHPLC–MS/MS Method for the Determination of Glaucocalyxin A, a Novel Potent Negative Akt Regulator in Rat Plasma, Lung and Brain Tissues: Application to a Pharmacokinetic Study

2019 ◽  
Vol 58 (3) ◽  
pp. 234-240
Author(s):  
Zhipeng Deng ◽  
Qian Liu ◽  
Jixiang He ◽  
Sixi Zhang ◽  
Wei Zhou
Keyword(s):  
Mass Spectrometry ◽  
Intravenous Administration ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Rat Plasma ◽  
Mass Spectrometry Analysis ◽  
Active Constituent ◽  
Limit Of Quantification ◽  
Relative Standard ◽  
Brain Tissues

Abstract Glaucocalyxin A, a novel potent negative Akt regulator, is a major active constituent of Rabdosia japonica. A simple, specific and sensitive ultra-high pressure liquid chromatography tandem mass spectrometry (UHPLC–MS/MS) method was developed and validated for the quantification of glaucocalyxin A in rat plasma, lung and brain tissues after intravenous administration. Sample preparation was carried out through a simple liqiud–liquid extraction with ethyl acetate using bullatine A as internal standard. The chromatographic separation was achieved by using an Agilent ZORBAX Eclipse Plus C18 column (3.0 mm × 100 mm, 1.8 μm) with a mobile phase of acetonitrile and water containing 0.1% formic acid in a gradient elution. Mass spectrometry analysis was conducted in positive ionization mode with multiple reaction monitoring transitions at m/z 333.2 → 157.1 for glaucocalyxin A and m/z 344.2 → 128.1 for IS. Calibration curves were linear over the ranges of 20.0–4000 ng/mL for both plasma and tissue samples (r2 > 0.99). The Lower limit of quantification (LLOQ) was 0.284 ng/mL. The intra-day and inter-day precision relative standard deviation (RSD%) were <14.9%, while the accuracy ranged from −12.5 to 17.0% for LLOQ and quality control samples. This UHPLC–MS/MS method was successfully applied in the pharmacokinetics, lung and brain tissue distributions of glaucocalyxin A after intravenous administration.

scholarly journals Sensitive Quantification of Liensinine Alkaloid Using a HPLC-MS/MS Method and Its Application in Microvolume Rat Plasma

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Fen Wei ◽  
Xilan Gou ◽  
Xiao Xu ◽  
Sicen Wang ◽  
Tao Bao
Keyword(s):  
Quality Control ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Rat Plasma ◽  
In Vivo Studies ◽  
Coefficient Of Determination ◽  
Ionization Source ◽  
Limit Of Quantification ◽  
Positive Mode

Liensinine, an important alkaloid in lotus seed, exhibits multiple functions such as anti-AIDS, anticancer, antidepressant, and antihypertensive properties. In this study, a highly sensitive HPLC-MS/MS method was developed and validated for the quantification of liensinine in microvolume rat plasma as low as 45 μL. Chromatographic separation was carried out using a reverse-phase Gemini-C18 column (100 mm × 3 mm i.d. × 5 μm), and mass selective detection using multiple reaction monitoring was attained using an electrospray ionization source, which operated in the positive mode. Dauricine was used as the internal standard. The precursor-to-product ion transition m/z 611.15 > 206.10 was selected for the detection of liensinine; m/z 625.25 > 206.10 was used for the detection of dauricine. The developed method is linear over the concentration range of 0.05–1000 ng/mL with an excellent coefficient of determination (R2 = 0.991). The recoveries ranged from 92.57% to 95.88% at three quality control levels. Intraday and interday precision and accuracy are less than 12.2% and 6.59%, respectively. The lower limit of quantification (LLOQ) is 0.05 ng/mL. The matrix effect was insignificant and acceptable. The validated method was successfully applied to the pharmacokinetic study of liensinine in rats. This method can be used for in vivo studies as well as quality control of traditional Chinese medicines and herbal tea containing liensinine alkaloid.

scholarly journals Determination of Anlotinib, a Tyrosine Kinase Inhibitor, in Rat Plasma by UHPLC-MS/MS and Its Application to a Pharmacokinetic Study

2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Zhe Wang ◽  
Le-jing Lian ◽  
Yan-yan Dong ◽  
Xiao Cui ◽  
Jian-chang Qian ◽  
...  
Keyword(s):  
Pharmacokinetic Study ◽  
Kinase Inhibitor ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Rat Plasma ◽  
Reaction Monitoring ◽  
Receptor Kinase ◽  
Quadrupole Mass ◽  
Triple Quadrupole Mass Spectrometer

Anlotinib is a novel inhibitor of receptor kinase tyrosine with multitargets and has a broad spectrum of inhibitory action on tumor angiogenesis and growth. A simple and rapid UHPLC-MS/MS bioanalytical method was validated for the determination of anlotinib in rat plasma, using imatinib as an internal standard. An Acquity BEH C18 column was used to separate analytes. The eluents consisted of formic acid/water (0.1 : 100, v/v) and acetonitrile with a mobile phase. A triple quadrupole mass spectrometer was operated for the quantification with multiple reaction monitoring (MRM) to determine transitions: 408.2 ⟶ 339.1 for anlotinib, and 494.3 ⟶ 394.1 for imatinib. The validated range was 0.1–50 ng/mL for anlotinib. Mean recovery rate of anlotinib in plasma was ≥99.32% and reproducible. Also, the intra- and interday precisions were both below 15%. This robust method was successfully applied to support the pharmacokinetic study of anlotinib in rats.

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