scholarly journals Quantification of Lappaconitine in Mouse Blood by UPLC-MS/MS and Its Application to a Pharmacokinetic Study

2019 ◽  
Vol 2019 ◽  
pp. 1-6
Author(s):  
Fan Chen ◽  
Xiuwei Shen ◽  
Peng Huang ◽  
Huiyan Fu ◽  
Yue Jin ◽  
...  
Keyword(s):  
Limit Of Detection ◽  
Multiple Reaction Monitoring ◽  
Ultrahigh Pressure ◽  
Absolute Bioavailability ◽  
Quantitative Detection ◽  
Intragastric Administration ◽  
Linear Calibration ◽  
Ionization Source ◽  
Mouse Blood ◽  
Limit Of Quantitation

Lappaconitine is extracted from Aconitum sinomontanum Nakai, which belongs to the Ranunculaceae. Lappaconitine is as a diterpenoid alkaloid used as a nonaddictive analgesic. To assure the rational use of the drug, ultrahigh-pressure liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was conducted to determine lappaconitine in mouse blood and its application to pharmacokinetics. In this study, khasianine was used as internet standard (IS). A UPLC BEH C18 column was used for chromatographic separation and the mobile phase consisted of acetonitrile and 10 mmol/L ammonium acetate (0.1% formic acid). The flow rate of was 0.4 mL/min. Quantitative detection was performed in a multiple reaction monitoring (MRM) mode using an electrospray ionization source in positive mode. Twenty-four mice were randomly divided into four groups, three of which received 2, 4, and 8 mg/kg lappaconitine by intragastric administration, while the other group received 1 mg/kg lappaconitine by intravenous administration. After 0.0833, 0.5, 1, 1.5, 2, 3, 4, and 8 h, blood samples were collected and acetonitrile was used for protein precipitation. A linear calibration relationship (R2 = 0.9979) in the range of 0.1-500 ng/mL in mouse blood indicated good results. The lower limit of quantitation was 0.1 ng/mL and the limit of detection was 0.04 ng/mL. The intra-day and inter-day precision were below 13% and 14%, respectively. The accuracy was 90.1-107.2%, and the recovery exceeded 81.1%. The matrix effect ranged between 102.1 and 108.8%. The absolute bioavailability of lappaconitine was 2.0%. UPLC-MS/MS achieved high sensitivity, speed, and selectivity. Methodological verification indicated this method as suitable for determination of lappaconitine in mouse blood.

scholarly journals Development of a rapid UPLC-MS/MS method for the determination of toddalolactone in mouse blood and its application in pharmacokinetics

2021 ◽  
Author(s):  
Jing Zhou ◽  
Hongzhe Wang ◽  
Caiyun Miao ◽  
Yunxi Yao ◽  
Jianshe Ma
Keyword(s):  
Matrix Effects ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Absolute Bioavailability ◽  
Quantitative Detection ◽  
Ionization Source ◽  
Mouse Blood ◽  
The Matrix ◽  
Product Ions

AbstractA rapid and simple UPLC-MS/MS method was developed to determine toddalolactone in mouse blood and applied to measure the pharmacokinetics of toddalolactone in mice. Blood samples were first preprocessed by ethyl acetate liquid-liquid extraction. Oxypeucedanin hydrate (internal standard, IS) and toddalolactone were gradient eluted from a UPLC BEH C18 column using a mobile phase consisting of acetonitrile and water (0.1% formic acid). Using electrospray ionization (ESI) as the ionization source, multiple reaction monitoring was used to detect the precursor and product ions of m/z 309.2 and 205.2, respectively, for toddalolactone and of m/z 305.1 and 203.0 for IS, respectively, for quantitative detection. A calibration curve was run over the concentration range of 5–4,000 ng/mL (r > 0.995). The matrix effects ranged from 93.5 to 98.4%, and the recovery was higher than 77.3%. The precision was less than 13%, and the accuracy ranged from 90.9 to 108.4%. The developed UPLC-MS/MS method was successfully used for measuring the pharmacokinetics of toddalolactone in mice after oral (20 mg/kg) and intravenous administration (5 mg/kg), and the absolute bioavailability of toddalolactone was 22.4%.

UPLC-MS/MS Method for Determination of Khasianine in Mouse Blood: Application for Its Pharmacokinetic Study

2020 ◽  
Vol 16 (6) ◽  
pp. 705-711
Author(s):  
Lianguo Chen ◽  
Qinghua Weng ◽  
Yijing Lin ◽  
Xiaojie Lu ◽  
Zuoquan Zhong ◽  
...  
Keyword(s):  
Lower Limit ◽  
Pharmacokinetic Study ◽  
Oral Absorption ◽  
Matrix Effects ◽  
Limit Of Detection ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Quantitative Detection ◽  
Mouse Blood ◽  
Limit Of Quantitation

Background: The aim of this study was to determine the concentrations of khasianine in mouse whole blood sample and its application for the pharmacokinetics by a rapid, selective and sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method. Methods: The blood samples were preprocessed by one-step protein precipitation with acetonitrile. The study was performed on an ACQUITY I-Class UPLC system with a UPLC BEH column. Lannaconitine (internal standard, IS) and khasianine were gradient eluted by a mixture of acetonitrile and water with 0.1% formic acid at a flow rate of 0.4 mL/min. The mass spectrometer was equipped with an Electrospray Ionization (ESI) source in positive mode. The quantitative detection was performed in a multiple reaction monitoring modes at transitions m/z 722.4→70.7 for khasianine and m/z 585.3→119.9 for the corresponding IS. Results: The calibration curve was of good linearity ranging from 0.5 to 1000 ng/mL (r > 0.995). The Lower Limit of Detection (LLOD) and Lower Limit of Quantitation (LLOQ) were 0.2 and 0.5 ng/mL, respectively. The inter-day and intra-day precision (RSD%) were both less than 14%, and the accuracy ranged from 86.6% to 108.3%. The matrix effects were between 98.0% and 103.7%, and the average recovery was better than 67.4%. Conclusion: This assay established a sensitive, rapid, selective UPLC-MS/MS method which was successfully used for the pharmacokinetic study of khasianine in mouse blood, and the absolute availability of khasianine was 0.78% which exhibited a poor oral absorption.

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 PERFORMANCE CHARACTERISTICS OF A FRET-BASED IMMUNOASSAY FOR QUANTITATION OF INFLIXIMAB ON A POINT-OF-CARE INSTRUMENT SYSTEM

2021 ◽  
Vol 27 (Supplement_1) ◽  
pp. S57-S57
Author(s):  
Edgar Ong ◽  
Ruo Huang ◽  
Richard Kirkland ◽  
Michael Hale ◽  
Larry Mimms
Keyword(s):  
Whole Blood ◽  
Limit Of Detection ◽  
Point Of Care ◽  
Quantitative Detection ◽  
Therapeutic Drug ◽  
Analytical Sensitivity ◽  
Sample Type ◽  
Hook Effect ◽  
Limit Of Quantitation ◽  
Assay Precision

Abstract Introduction A fast (<5 min), time-resolved fluorescence resonance energy transfer (FRET)-based immunoassay was developed for the quantitative detection of infliximab (IFX) and biosimilars for use in therapeutic drug monitoring using only 20 µL of fingerstick whole blood or serum at the point-of-care. The Procise IFX assay and ProciseDx analyzer are CE-marked. Studies were performed to characterize analytical performance of the Procise IFX assay on the ProciseDx analyzer. Methods Analytical testing was performed by spiking known amounts of IFX into negative serum and whole blood specimens. Analytical sensitivity was determined using limiting concentrations of IFX. Linearity was determined by testing IFX across the assay range. Hook effect was assessed at IFX concentrations beyond levels expected to be found within a patient. Testing of assay precision, cross-reactivity and potential interfering substances, and biosimilars was performed. The Procise IFX assay was also compared head-to-head with another CE-marked assay: LISA-TRACKER infliximab ELISA test (Theradiag, France). The accuracy of the Procise IFX assay is established through calibrators and controls traceable to the WHO 1st International Standard for Infliximab (NIBSC code: 16/170). Results The Procise IFX assay shows a Limit of Blank, Limit of Detection, and Lower Limit of Quantitation (LLoQ) of 0.1, 0.2, and 1.1 µg/mL in serum and 0.6, 1.1, and 1.7 µg/mL in whole blood, respectively. The linear assay range was determined to be 1.7 to 77.2 µg/mL in serum and whole blood. No hook effect was observed at an IFX concentration of 200 µg/mL as the value reported as “>ULoQ”. Assay precision testing across 20 days with multiple runs and reagent lots showed an intra-assay coefficient of variation (CV) of 2.7%, an inter-assay CV of <2%, and a total CV of 3.4%. The presence of potentially interfering/cross-reacting substances showed minimal impact on assay specificity with %bias within ±8% of control. Testing of biosimilars (infliximab-dyyb and infliximab-abda) showed good recovery. A good correlation to the Theradiag infliximab ELISA was obtained for both serum (slope=1.01; r=0.99) and whole blood (slope=1.01; r=0.98) samples (Figure 1). Conclusion Results indicate that the Procise IFX assay is sensitive, specific, and precise yielding results within 5 minutes from both whole blood and serum without the operator needing to specify sample type. Additionally, it shows very good correlation to a comparator assay that takes several hours and sample manipulation to yield results. This makes the Procise IFX assay ideal for obtaining fast and accurate IFX quantitation, thus allowing for immediate drug level dosing decisions to be made by the physician during patient treatment.

Simultaneous Determination of Four Herbicide and Pesticide Residues in Chinese Green Tea Using QuEChERS Purification Procedure and UPLC-MS/MS Analysis

2013 ◽  
Vol 634-638 ◽  
pp. 1586-1590
Author(s):  
Su Fang Wang ◽  
Shou Jie Zhang ◽  
Chun Hong Dong ◽  
Guo Qing Wang ◽  
Jun Feng Guo ◽  
...  
Keyword(s):  
Formic Acid ◽  
Simultaneous Determination ◽  
Green Tea ◽  
Limit Of Detection ◽  
Multiple Reaction Monitoring ◽  
Graphitized Carbon Black ◽  
Ms Analysis ◽  
Relative Standard ◽  
Limit Of Quantitation

A method for simultaneous determination of residuals of four herbicides and pesticides, simazine, carboxin, diflubenzuron and rotenone, in Chinese green tea was developed. In the proposed method, the tea powder was placed in a centrifuge tube with a plug, extracted in saturated aqueous sodium chloride solution and acetonitrile, agitated using vortex oscillator, and then centrifuged 5 min at 4000 rpm. The supernatant solution was purified by primary secondary amine (PSA) sorbent, C18 power, and graphitized carbon black powder, respectively. Then the purified extracts were dissolved with acetonitrile:0.1% formic acid aqueous solution (40:60, V/V) and agitated, filtered using a syringe with 0.22 μm nylon filter prior to UPLC-MS/MS analysis. The UPLC analysis was performed on an ACQUITY UPLC® HSS T3 column (2.1 mm×100 mm, 1.8 µm), using acetonitrile-0.1% formic acid as mobile phase with the flow rate as 0.3 mL•min-1. Injection volume was 10 µL. Positive ionization mode was applied, and the ions were monitored in the multiple reaction monitoring (MRM) mode with curtain gas 0.069 MPa, collision gas 0.052 MPa, ESI ion spray voltage 5000 V, temperature 550 °C, nebulizer gas 0.24 MPa, and turbo gas 0.28 MPa. The limit of detection (LOD) and limit of quantitation (LOQ) of the proposed method are 1 μg•kg-1and 5 μg•kg-1, respectively. The average recoveries of the four pesticides at 10, 20, and 50 µg•kg-1spiking levels range from 77.4% to 95.3%. TheSupersSuperscript textcript textrelative standard deviation (RSD) (n=6) range form 11.83% to 4.52%.

scholarly journals Determination of Tianeptine in Tablets by High-Performance Liquid Chromatography with Fluorescence Detection

2007 ◽  
Vol 90 (3) ◽  
pp. 720-724
Author(s):  
Sevgi Tatar Ulu
Keyword(s):  
Lower Limit ◽  
High Performance ◽  
Limit Of Detection ◽  
Internal Standard ◽  
Linear Calibration ◽  
Fluorescence Detector ◽  
Relative Standard ◽  
Validation Parameters ◽  
Limit Of Quantitation

Abstract A sensitive and selective high-performance liquid chromatographic method has been developed for the determination of tianeptine (Tia) in tablets. The method is based on derivatization of Tia with 4-chloro-7-nitrobenzofurazan (NBD-Cl). A mobile phase consisting of acetonitrile10 mM orthophosphoric acid (pH 2.5; 77 + 23) was used at a flow rate of 1 mL/min on a C18 column. The Tia-NBD derivative was monitored using a fluorescence detector, with emission set at 520 nm and excitation at 458 nm. Gabapentin was selected as an internal standard. Linear calibration graphs were obtained in the concentration range of 45300 ng/mL. The lower limit of detection (LOD) was 10 ng/mL at a signal-to-noise ratio of 4. The lower limit of quantitation (LOQ) was 45 ng/mL. The relative standard values for intra- and interday precision were <0.46 and <0.57%, respectively. The recovery of the drug samples ranged between 98.89 and 99.85%. No chromatographic interference from the tablet excipients was found. The proposed method was validated in terms of precision, robustness, recovery, LOD, and LOQ. All the validation parameters were within the acceptance range. The proposed method was applied for the determination of Tia in commercially available tablets. The results were compared with those obtained by an ultraviolet spectrophotometric method using t- and F-tests.

scholarly journals Pharmacokinetics and bioavailability of liensinine in mouse blood by UPLC-MS/MS

2020 ◽  
Author(s):  
Shuhua Tong ◽  
Yuqi Zeng ◽  
Jianshe Ma ◽  
Congcong Wen
Keyword(s):  
Pharmacokinetic Study ◽  
Mobile Phase ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Quantitative Detection ◽  
Reaction Monitoring ◽  
Mouse Blood ◽  
Blood Samples ◽  
The Matrix ◽  
Better Than

AbstractLiensinine is a bisbenzyltetrahydroisoquinoline alkaloid extracted from lotus (Nelumbo nucifera GAERTNER., Nelumbonaceae), especially in its embryo loti “Lien Tze Hsin” (green embryo of mature seed). A rapid and simple UPLC-MS/MS method was developed to determine liensinine in mouse blood and its application to a pharmacokinetic study. The blood samples were preprocessed by protein precipitation using acetonitrile. Midazolam (internal standard, IS) and liensinine were gradient eluted by mobile phase of methanol and water (0.1% formic acid) in a Waters UPLC BEH C18 column. The multiple reaction monitoring of m/z 611.3 → 206.1 for liensinine and m/z 326.2 → 291.1 for IS with an electrospray ionization (ESI) source was used for quantitative detection. The calibration curve ranged from 0.5 to 400 ng/mL (r > 0.995). The accuracy ranged from 92.2 to 108.2%, the precision of intra-day and inter-day was less than 14%, and the matrix effect was between 100.0% and 109.6%, the recovery was better than 71.0%. The developed UPLC-MS/MS method was successfully used for a pharmacokinetic study of liensinine in mice after oral (5 mg/kg) and intravenous administration (1 mg/kg), and the absolute availability of liensinine was 1.8%.

scholarly journals Pharmacokinetic UPLC–MS/MS studies on byakangelicol after oral and intravenous administration to rats

2020 ◽  
Vol 32 (1) ◽  
pp. 49-52
Author(s):  
Xi Bao ◽  
Bingge Huang ◽  
Yiting Mao ◽  
Zhiguang Zhang ◽  
Yunfang Zhou ◽  
...  
Keyword(s):  
Liquid Chromatography ◽  
Multiple Reaction Monitoring ◽  
A549 Cells ◽  
Internal Standard ◽  
Ultra Performance Liquid Chromatography ◽  
Rat Plasma ◽  
Absolute Bioavailability ◽  
Dependent Manner ◽  
Limit Of Quantitation ◽  
Intravenous And Oral Administration

Byakangelicol is one of coumarins from Baizhi and has been shown to inhibit the release of PGE2 from human lung epithelial A549 cells in a dose-dependent manner. A sensitive ultra-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) method was developed and full validated for the quantification of byakangelicol in rat plasma. The pharmacokinetics of byakangelicol after both intravenous (5 mg/kg) and oral (15 mg/kg) administrations were studied. Chromatographic separation was performed on an ultra-performance liquid chromatography ethylene bridged hybrid (UPLC BEH) C18 column with acetonitrile and 0.1% formic acid as the mobile phase at a flow rate of 0.4 mL/min; fargesin was used as the internal standard (IS). The following quantitative analysis of byakangelicol was utilized in the multiple reaction monitoring mode. The samples were extracted from rat plasma via protein precipitation using acetonitrile. In the concentration range of 1–2000 ng/mL, the method correlated linearity (r > 0.995) with a lower limit of quantitation (LLOQ) of 1 ng/mL. Intra-day precision was less than 11%, and inter-day precision was less than 12%. The accuracy was between 92.0% and 108.7%, the recovery was better than 89.6%, and the matrix effect was between 85.9% and 98.6%. The method was successfully applied to a pharmacokinetic study of byakangelicol after intravenous and oral administration, and the absolute bioavailability was 3.6%.

scholarly journals An Efficient Heparin Affinity Column Purification Method Coupled with Ultraperformance Liquid Chromatography for the Quantification of Native Lactoferrin in Breast Milk

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Huizhi Yuan ◽  
Na Li ◽  
Yiping Xun ◽  
Lin Wang ◽  
Xiaoying Feng ◽  
...  
Keyword(s):  
Liquid Chromatography ◽  
Breast Milk ◽  
Human Milk ◽  
Limit Of Detection ◽  
Affinity Column ◽  
Linear Calibration ◽  
Step Method ◽  
Purification Method ◽  
Limit Of Quantitation ◽  
Heparin Affinity

Lactoferrin (LF) is a bioactive multifunctional protein and found in the highest amounts in human milk. Several methods can be used to quantify LF. However, quantification of native LF has garnered relatively little interest to date. This study aimed to develop a novel efficient two-step method for quantifying native LF in breast milk. During the analysis, LF was first extracted with phosphate buffer (pH 5.0), purified using a heparin affinity column. Subsequently, LF was detected using ultraperformance liquid chromatography (UPLC) at a wavelength of 201 nm. A linear calibration curve was obtained in the range of 5–200 mg/L. The limit of detection and limit of quantitation were 1 mg/L and 5 mg/L, respectively, indicating that the validated method could be employed to quantify LF in breast milk. Compared with previous HPLC methods, this method demonstrated several remarkable advantages, including simple operation, low-cost detection, and high accuracy. Hence, the results demonstrate an efficient method that can be employed commercially to purify and analyze LF in human milk samples.

Simultaneous Quantitation of Seven Phenethylamine-Type Drugs in Forensic Blood and Urine Samples by UHPLC–MS-MS

2021 ◽  
Author(s):  
Chu-An Yang ◽  
Hsiu-Chuan Liu ◽  
Ray H Liu ◽  
Dong-Liang Lin ◽  
Shu-Pao Wu
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Tandem Mass Spectrometry ◽  
Limit Of Detection ◽  
Multiple Reaction Monitoring ◽  
Analytical Data ◽  
Tandem Mass ◽  
Limit Of Quantitation ◽  
Routine Identification ◽  
Urine Specimens

Abstract Abuse of new psychoactive substances (NPS) has become a health and social issue of global concern. p-Methoxyamphetamine (PMA)/p-methoxymethamphetamine (PMMA) with fluoro- or chloro-derivatives of amphetamine and methamphetamine were among the most common drugs found in specimens from fatal cases in Taiwan during the January 2011 to December 2018 period. A liquid–liquid extraction sample preparation protocol with highly sensitive ultra-high performance liquid chromatography–tandem mass spectrometry approach was developed for the simultaneous analysis of seven phenethylamine-type drugs—PMA, PMMA, p-methoxyethylamphetamine, 4-fluoroamphetamine (4-FA), 4-fluoromethamphetamine (4-FMA), 4-chloroamphetamine (4-CA) and 4-chloromethamphetamine (4-CMA)—in postmortem blood and urine specimens. Separation by liquid chromatography was performed by Agilent Zorbax SB-Aq column. Tandem mass spectrometry was operated in Agilent Jet Stream Technology electrospray ionization in positive-ion multiple reaction monitoring mode. An analytical methodology was evaluated using drug-free blood and urine after fortification with 100–2,000 ng/mL of the seven target analytes. Average extraction recoveries were >80%; slightly higher ion suppression was observed for PMA and 4-CA; intra-/inter-day precision (% coefficient of variation) and accuracy were in the ranges of 0.52–12.3% and 85–110%, respectively. Limit of detection and lower limit of quantitation for these seven analytes were both in the 0.5–5 ng/mL range. Interference and carryover were not significant. This relatively simple methodology was found effective and reliable for routine identification and quantitation of these seven analytes in postmortem and antemortem blood and urine specimens received in 2018. Analytical data obtained from these actual cases indicated the following: (i) compared to findings reported during the 2007–2011 period, the use of substituted phenethylamine-type drugs decreased in 2018; (ii) ketamine and 7-aminonimetazepam (the main metabolite of nimetazepam) were the most common co-ingested substances in specimens containing PMA/PMMA, 4-FA/4-FMA, or 4-CA/4-CMA; and (iii) in drug fatalities, the concentration of PMA was significantly higher than the concentration of PMMA in both urine and blood, while the reverse was true in urine specimens from antemortem cases.

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