Pharmacokinetic Study of Deltaline in Mouse Blood Based on UPLCMS/ MS

2019 ◽  
Vol 15 (2) ◽  
pp. 194-199 ◽  
Author(s):  
Huanchun Song ◽  
Yiwei Huang ◽  
Dongqing Zhu ◽  
Shuhua Tong ◽  
Meiling Zhang ◽  
...  
Keyword(s):  
Intravenous Administration ◽  
Pharmacokinetic Study ◽  
Internal Standard ◽  
Gradient Elution ◽  
Ultra Performance Liquid Chromatography ◽  
Mouse Blood ◽  
Limit Of Quantitation ◽  
The Matrix ◽  
Liquid Chromatography Tandem Mass ◽  
Precipitate Protein

Introduction: Deltaline, an aconitine-type alkaloid, was detected in mouse blood using an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method, and the pharmacokinetics of deltaline following intravenous administration in mice was studied. </P><P> Materials and Methods: The gelsenicine was used as the internal standard (IS). Deltaline and IS were eluted at a flow rate of 0.4 ml/min and separated on a UPLC BEH C18 column by gradient elution using acetonitrile and 10 mmol/L ammonium acetate (0.1% formic acid) as a mobile phase. The following transitions were obtained at m/z 508.2→75.0 for deltaline and m/z 327.1→107.8 for gelsenicine in multiple reactions monitoring mode. Acetonitrile was used to precipitate protein. Six mice after intravenous administration of a single dose of deltaline (1 mg/kg), 20-µL blood samples from each mouse were collected from the tail vein. Results: The UPLC-MS/MS method was sensitive and linear (r>0.995) with a lower limit of quantitation (LLOQ) of 0.1 ng/mL over the range of 0.1-500 ng/mL. Intra- and inter-day precisions were below 13%, the accuracy range was between 88.0% and 108.2%, the recovery was higher than 90.1%, and the matrix effect was between 102.9% and 108.1%. Conclusion: The method was sensitive, fast, specific, and has been successfully applied to a pharmacokinetic study of deltaline after intravenous administration.

scholarly journals Pharmacokinetics and UPLC-MS/MS of Delsoline in Mouse Whole Blood

2018 ◽  
Vol 2018 ◽  
pp. 1-7
Author(s):  
Lingjiu Shao ◽  
Yue Jin ◽  
Huiyan Fu ◽  
Jianshe Ma ◽  
Xianqin Wang ◽  
...  
Keyword(s):  
Muscle Tension ◽  
Internal Standard ◽  
Gradient Elution ◽  
Absolute Bioavailability ◽  
Intragastric Administration ◽  
Mouse Blood ◽  
Relative Standard ◽  
Limit Of Quantitation ◽  
The Matrix ◽  
Liquid Chromatography Tandem Mass

Delsoline, a major alkaloid of Delphinium anthriscifolium Hance, has both a curare-like effect and a ganglion-blocking effect and is used to relieve muscle tension or hyperkinesia. A ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was established for the determination of delsoline in mouse blood, and the pharmacokinetics of delsoline after intravenous administration (1 mg/kg) and intragastric administration (9, 6, and 3 mg/kg) were studied. Gelsenicine served as an internal standard, and a UPLC BEH C18 chromatographic column was used. The mobile phase consisted of acetonitrile and 0.1% formic acid; the gradient elution flow rate was 0.4 mL/min. The MRM model was used for the quantitative analysis of delsoline m/z 468.3⟶108.1 and the internal standard m/z 327.1⟶296.1. Mouse blood samples were treated with acetonitrile precipitation to remove proteins. In the concentration range of 0.1–1000 ng/mL, delsoline in mouse blood showed a good linearity (r2 > 0.995), and the lower limit of quantitation was 0.1 ng/mL. The intraday precision relative standard deviation (RSD) was below 14%, and the interday precision RSD was below 15%. The accuracy ranged between 94.3% and 110.1%, the average recovery was above 90.8%, and the matrix effect ranged between 97.0% and 102.5%. The UPLC-MS/MS method was sensitive, rapid, and selective in the study of pharmacokinetics of delsoline. The absolute bioavailability of delsoline was 20.9%.

scholarly journals Pharmacokinetics of ebeiedinone in mouse blood by UPLC–MS/MS

2020 ◽  
Vol 32 (3) ◽  
pp. 194-198
Author(s):  
Yongxi Jin ◽  
Yuyan Chen ◽  
Jiawen Liu ◽  
Xi Bao ◽  
Yinghao Zhi ◽  
...  
Keyword(s):  
Pharmacokinetic Study ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Ultra Performance Liquid Chromatography ◽  
Absolute Bioavailability ◽  
Mouse Blood ◽  
Limit Of Quantification ◽  
Chromatography Tandem Mass Spectrometry ◽  
The Matrix ◽  
Liquid Chromatography Tandem Mass

An ultra-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) method was established to determine ebeiedinone in mouse blood, and the pharmacokinetics of ebeiedinone after intravenous (0.5 mg/kg) and oral (2, 4, and 8 mg/kg) administration was studied. Twenty-four mice were randomly divided into 4 groups, 1 group was for intravenous administration (0.5 mg/kg), and other 3 groups were for oral administration (2, 4, and 8 mg/kg), with 6 rats in each group. Yubeinine was used as an internal standard. Multiple reaction monitoring (MRM) mode was used to quantitatively analyzed ebeiedinone m/z 414.4 → 91.1 and the internal standard m/z 430.4 → 412.3 in the electrospray ionization (ESI) positive interface. In the concentration range of 1–2000 ng/mL, the ebeiedinone in the mouse blood was linear (r2 > 0.995), and the lower limit of quantification was 1.0 ng/mL. In the mouse blood, the intra-day precision coefficient of variation (CV) was less than 15%, and the inter-day precision CV was less than 15%. The accuracy ranged from 85.4% to 114.6%, and the average recovery was higher than 61.3%. The matrix effect was between 87.0% and 106.5%. These data met the pharmacokinetic study requirements of ebeiedinone. The UPLC–MS/MS method was sensitive, rapid, and selective and was successfully applied to the pharmacokinetic study of ebeiedinone in mice. The absolute bioavailability of ebeiedinone was 30.6%.

scholarly journals A Novel UPLC-MS/MS Assay for the Measurement of Linezolid and its Metabolite PNU-142300 in Human Serum and its Application to Patients With Renal Insufficiency

2021 ◽  
Vol 12 ◽  
Author(s):  
Yingying Wang ◽  
Er-min Gu ◽  
Xiaoxiang Du ◽  
Ren-ai Xu ◽  
Guanyang Lin
Keyword(s):  
Liquid Chromatography ◽  
Renal Insufficiency ◽  
Human Serum ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Gradient Elution ◽  
Ultra Performance Liquid Chromatography ◽  
Serum Samples ◽  
The Matrix ◽  
Liquid Chromatography Tandem Mass

The contribution of the metabolites of linezolid to the associated myelosuppression is unknown in patients who are renal impairment. In this research, the purpose of our experiment was to explore and develop a quick and robust ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) assay for the determination of linezolid and its metabolite PNU-142300 in human serum simultaneously. The analytes were prepared using a simple and convenient approach with acetonitrile for protein crash, and then separated from the matrix on a Waters Acquity Ultra performance liquid chromatography (UPLC) BEH C18 (2.1 mm × 50 mm, 1.7 μm) column in a program of gradient elution, where the mobile phase was consisted of water with 0.1% formic acid and acetonitrile, and was placed at 0.40 ml/min flow rate. Multiple reaction monitoring (MRM) was employed and conducted for UPLC-MS/MS detection with ion transitions at m/z 338.01 → 296.03 for linezolid, m/z 369.96 → 327.98 for PNU-142300 and m/z 370.98 → 342.99 for tedizolid (Internal standard, IS), respectively. This method had good linearity respectively in the calibration range of 0.01–20 μg/ml for linezolid, and 0.05–100 μg/ml for PNU-142300. In the intra- and inter-day, the precision of linezolid and PNU-142300 was below 14.2%, and the accuracy in this method was determined to be from −9.7 to 12.8%. In addition, recovery and matrix effect of the analytes were all found to be acceptable, and the analytes during the assay and storage in serum samples were observed to be stable. The novel optimized UPLC-MS/MS assay was also successfully employed to determine the concentration levels of linezolid and PNU-142300 in human serum. The results showed that linezolid-associated myelosuppression occurs more frequently in patients with renal insufficiency, and the metabolite-to-parent concentration ratio of PNU-142300 is predicted to reduce this toxicity of myelosuppression.

scholarly journals Determination of eugenitin in mouse blood by ultra-performance liquid chromatography-tandem mass spectrometry and its application to a pharmacokinetic study

2021 ◽  
Author(s):  
Chongliang Lin ◽  
Dezhen Song ◽  
Haodong Jiang ◽  
Lvqi Luo ◽  
Xi Bao ◽  
...  
Keyword(s):  
Biological Fluids ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Ultra Performance Liquid Chromatography ◽  
Quantitative Detection ◽  
Syzygium Aromaticum ◽  
Mouse Blood ◽  
The Matrix ◽  
Liquid Chromatography Tandem Mass

Abstract Eugenitin is a non-volatile chromone derivative which is always found in dried flower buds of Syzygium aromaticum L. (Merr.) & L.M. Perry. Until now, there were no reports about the pharmacokinetics of eugenitin in biological fluids. A UPLC-MS/MS method developed to determine eugenitin in mouse blood. The blood samples were prepared by protein precipitation with acetonitrile. Chrysin (internal standard, IS) and eugenitin were gradient eluted by mobile phase of acetonitrile and water (0.1% formic acid) in a BEH C18 column. The multiple reaction monitoring (MRM) of m/z 221.1→206.0 for eugenitin and m/z 255.1→152.9 for IS with an electrospray ionization (ESI) source was used for quantitative detection. The calibration curve ranged from 0.5 to 500 ng/mL (r > 0.995). The accuracy ranged from 98 to 113%, the precision was less than 12%, and the matrix effect was between 86 and 94%, the recovery was better than 81%. The developed method was successfully used for pharmacokinetics of eugenitin in mice after intravenous (5 mg/kg) and oral (20 mg/kg) administration, and the absolute availability of eugenitin was 12%.

scholarly journals Simultaneous Determination of Six Uncaria Alkaloids in Mouse Blood by UPLC–MS/MS and Its Application in Pharmacokinetics and Bioavailability

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Lianguo Chen ◽  
Jianshe Ma ◽  
Xianqin Wang ◽  
Meiling Zhang
Keyword(s):  
Simultaneous Determination ◽  
Oral Absorption ◽  
Matrix Effects ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Gradient Elution ◽  
Mouse Blood ◽  
The Matrix ◽  
Liquid Chromatography Tandem Mass

A specific ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method has been developed for the simultaneous determination of six Uncaria alkaloids in mouse blood with midazolam as the internal standard (IS). Only 20 μL blood was needed for sample preparation, and the protein was precipitated with acetonitrile. The UPLC BEH C18 column (2.1 mm×100 mm, 1.7 μm) was used for chromatographic separation. The mobile phase consisted of 0.1% formic acid and acetonitrile with gradient elution within 5.5 min. Multiple reaction monitoring (MRM) and the positive electrospray ionization model were used for quantitative analysis. The accuracy of the UPLC-MS/MS method ranged from 86.5% to 110.4%. The precision for intraday and interday was ≤15% each. The mean recovery and the matrix effects were found to be 64.4-86.8% and 94.1-109.4%, respectively. The calibration curves in blood were linear in the range of 1-1000 ng/mL with a favorable correlation coefficient (r2) of 0.995. The pharmacokinetic results showed that six Uncaria alkaloids metabolized rapidly in mice with a half-life between 0.6 h and 4.4 h. The bioavailability of corynoxeine, isocorynoxeine, rhynchophylline, isorhynchophylline, hirsutine, and hirsuteine was 27.3%, 32.7%, 49.4%, 29.5%, 68.9%, and 51.0%, respectively, which showed satisfactory oral absorption of each alkaloid.

scholarly journals Determination of narciclasine in mouse blood by UPLC-MS/MS and its application to a pharmacokinetic study

2021 ◽  
Author(s):  
Ke Ren ◽  
Tiantian Feng ◽  
Hai Shi ◽  
Jianshe Ma ◽  
Yongxi Jin
Keyword(s):  
Intravenous Administration ◽  
Pharmacokinetic Study ◽  
Mobile Phase ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Hydroxy Derivative ◽  
Reaction Monitoring ◽  
Mouse Blood ◽  
The Matrix

AbstractNarciclasine is a 7-hydroxy derivative of lycorisidine. It was the first alkaloid isolated from the stem of narcissus (Amaryllidaceae) in 1967. Six mice were given narciclasine (5 mg/kg) by intravenous administration. A UPLC-MS/MS method was developed to determine narciclasine in mouse blood. Tectorigenin (internal standard, IS) and narciclasine were gradient eluted by mobile phase of methanol and 0.1% formic acid in a BEH C18 column. The multiple reaction monitoring (MRM) of m/z 308.1→248.1 for narciclasine and m/z 301.1→286.0 for IS with an electrospray ionization (ESI) source was used for quantitative determination. The calibration curve ranged from 1 to 6,000 ng/mL. The accuracy was from 92.5 to 107.3%, and the matrix effect was between 103.6 and 107.4%. The developed UPLC-MS/MS method was successfully applicated to a pharmacokinetic study of narciclasine in mice after intravenous administration (5 mg/kg).

scholarly journals Pharmacokinetics of tectorigenin, tectoridi, irigenin, and iridin in mouse blood after intravenous administration by UPLC-MS/MS

2021 ◽  
Author(s):  
Jianbo Li ◽  
Yuqi Yao ◽  
Minyue Zhou ◽  
Zheng Yu ◽  
Yinan Jin ◽  
...  
Keyword(s):  
Intravenous Administration ◽  
Detection Method ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Gradient Elution ◽  
Reaction Monitoring ◽  
Mouse Blood ◽  
Target Analytes ◽  
The Matrix ◽  
Positive Ion

AbstractTectorigenin, tectoridin, irigenin, and iridin are the four most predominant compounds present in She Gan. She Gan has been used in traditional Chinese medicine because of its anti-inflammatory, hepatoprotective, anti-tumor, antioxidant, phytoestrogen-like properties. In this paper, a UPLC-MS/MS method was developed to measure the pharmacokinetics of tectorigenin, tectoridin, irigenin, iridin after intravenous administration in mice. A UPLC BEH C18 (50 mm × 2.1 mm, 1.7 μm particle size) chromatographic column was utilized for separation of the four target analytes and internal standard (IS), and the analysis of blood plasma samples; the mobile phase consisted of an acetonitrile-water (w/0.1% formic acid) gradient elution. Electron spray ionization (ESI) positive-ion mode and multiple reaction monitoring (MRM) mode was used for quantitative analysis of the analytes and internal standard. The four compounds were administered intravenously (sublingual) at doses of 5 mg/kg. After blood sampling, samples were processed and then analyzed by UPLC-MS/MS. The linearity of the method was robust over the concentration range of 2–5,000 ng/mL. The intra-day precision of the analysis was within 15%, the inter-day precision was within 12%, and the accuracy was between 92% and 110%. The recoveries were 65–68%, and the matrix effect was 93–109%. The established UPLC-MS/MS detection method was then successfully applied to study the pharmacokinetics of tectorigenin, tectoridin, irigenin, iridin in mice.

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 A New UPLC-MS/MS Method Validated for Quantification of Jervine in Rat Plasma and the Study of Its Pharmacokinetics in Rats

2019 ◽  
Vol 2019 ◽  
pp. 1-6 ◽  
Author(s):  
Lianguo Chen ◽  
Qinghua Weng ◽  
Jianshe Ma
Keyword(s):  
Lower Limit ◽  
Internal Standard ◽  
Rat Plasma ◽  
Pharmacokinetic Parameters ◽  
Limit Of Determination ◽  
Limit Of Quantitation ◽  
The Matrix ◽  
Liquid Chromatography Tandem Mass ◽  
Reactive Monitoring ◽  
Interday Precision

The aim of this study was to develop an ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method to assess the concentration of jervine in rat plasma and its pharmacokinetics. Diazepam was used as internal standard (IS). The chromatographic separation of jervine and IS was carried out on an UPLC BEH C18 column (2.1 mm × 50 mm, 1.7 μm) with a flow rate of 0.4 mL/min. A mixture of acetonitrile and water (0.1% formic acid) was used as a mobile phase. The UPLC-MS/MS was equipped with an electrospray ionization (ESI), adopting multiple reactive monitoring mode to determine jervine in rat plasma. The retention times of jervine and the internal standard were 1.71 and 2.13 min, respectively. The calibration curve of jervine ranged between 1 and 1000 ng/mL. The lower limit of quantitation (LLOQ) was 1 ng/mL, and the lower limit of determination (LLOD) was 0.2 ng/mL. The accuracy was ±6%; the interday precision and intraday precision were no more than 9%. The recovery was higher than 90.3%, and the matrix effect was lower than 10%. The UPLC-MS/MS method was successfully developed and used for the application of the pharmacokinetic study. The primary pharmacokinetic parameters of jervine in this study were as follows: the AUC(0–∞) was 969.3 ± 277.7 ng/mL·h, the Cmax was 506.6 ± 192.8 ng/mL, the CL/F was 1.7 ± 0.5 L/h/kg, and the t1/2 was 3.4 ± 1.2 h.

scholarly journals Development and validation of a rapid UHPLC-MS/MS method for the determination of fenofibric acid in human plasma: Application to a pharmacokinetic study of fenofibrate tablet in Chinese subjects

2020 ◽  
Author(s):  
Xiaorong Wu ◽  
Yankai Wang ◽  
Binbin Liang ◽  
Honghai Wu ◽  
Liying Wu ◽  
...  
Keyword(s):  
Human Plasma ◽  
Pharmacokinetic Study ◽  
High Performance ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Fenofibric Acid ◽  
The Matrix ◽  
Liquid Chromatography Tandem Mass ◽  
Development And Validation ◽  
Chinese Subjects

AbstractAn ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC–MS/MS) method was developed to determine the fenofibric acid (FA) in human plasma and applied to a pharmacokinetic study of fenofibrate tablet (Lipanthyl® supra, 160 mg) on Chinese subjects which had not been reported. Bezafibrate was used as an internal standard (IS), and the plasma samples were precipitated by methanol. Multiple reaction monitoring (MRM) mode was used to quantitatively analyzed FA m/z 317.2 → 230.7 and the IS m/z 360.0 → 274.0 in the electrospray ionization (ESI) negative interface. The calibration curves were linear over the range of 50–30,000  ng/mL (r2  ≥  0.996). The intra-day and inter-day precision (coefficient of variation, CV%) was less than 2.7 and 2.5%, respectively. The accuracy (relative error, RE%) ranged from −4.5 to 6.9%. The average recovery was higher than 86.2%, and the matrix effect was between 95.32 and 110.55%. The simple, rapid, and selectivity method was successfully applied to the pharmacokinetic study of fenofibrate tablets on Chinese subjects.

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