scholarly journals An Accurate and Effective Method for Measuring Osimertinib by UPLC-TOF-MS and Its Pharmacokinetic Study in Rats

Molecules ◽  
2018 ◽  
Vol 23 (11) ◽  
pp. 2894 ◽  
Author(s):  
Song-Tao Dong ◽  
Ying Li ◽  
Hao-Tian Yang ◽  
Yin Wu ◽  
Ya-Jing Li ◽  
...  
Keyword(s):  
Matrix Effects ◽  
Internal Standard ◽  
Ultra Performance Liquid Chromatography ◽  
Rat Plasma ◽  
Analysis Method ◽  
T790m Mutation ◽  
Flight Mass Spectrometry ◽  
Relative Standard ◽  
New Generation ◽  
Tof Ms

Osimertinib, a new-generation inhibitor of the epidermal growth factor, has been used for the clinical treatment of advanced T790M mutation-positive tumors. In this research, an original analysis method was established for the quantification of osimertinib by ultra-performance liquid chromatography with time of flight mass spectrometry (UPLC-TOF-MS) in rat plasma. After protein precipitation with acetonitrile and sorafinib (internal standard, IS), they were chromatographed through a Waters XTerra MS C18 column. The mobile phase was acetonitrile and water (including 0.1% ammonia). The relative standard deviation (RSD) of the intra- and inter-day results ranged from 5.38 to 9.76% and from 6.02 to 9.46%, respectively, and the extraction recovery and matrix effects were calculated to range from 84.31 to 96.14% and from 91.46 to 97.18%, respectively. The results illustrated that the analysis method had sufficient specificity, accuracy and precision. Meanwhile, the UPLC-TOF-MS method for osimertinib was successfully applied into the pharmacokinetics of SD rats.

scholarly journals Determination of Lekethromycin, a Novel Macrolide Lactone, in Rat Plasma by UPLC-MS/MS and Its Application to a Pharmacokinetic Study

Molecules ◽  
2020 ◽  
Vol 25 (20) ◽  
pp. 4676
Author(s):  
Hongzhi Xiao ◽  
Pan Sun ◽  
Jicheng Qiu ◽  
Jianzhong Wang ◽  
Lei Yan ◽  
...  
Keyword(s):  
Electrospray Ionization ◽  
Matrix Effects ◽  
High Resolution Mass Spectrometry ◽  
Internal Standard ◽  
Gradient Elution ◽  
Storage Conditions ◽  
Rat Plasma ◽  
Pharmacokinetic Parameters ◽  
Limit Of Quantification ◽  
Relative Standard

Lekethromycin, a new macrolide lactone, exhibits significant antibacterial activity. In this study, a reliable analytical ultrahigh-performance liquid chromatography electrospray ionization quadrupole Orbitrap high-resolution mass spectrometry (UPLC-ESI-Orbitrap-MS) method was established and validated for the detection of lekethromycin in rat plasma. After a simple acetonitrile (ACN)-mediated plasma protein precipitation, chromatographic separation was performed on a Phenomenex Luna Omega PS C18 column (30 × 2.1 mm i.d. particle size = 3 μm) conducted in a gradient elution procedure using 0.5% formic acid (FA) in ACN and 0.5% FA in water as the mobile phase pumped at a flow rate of 0.3 mL/min. Detection was carried out under positive electrospray ionization (ESI+) conditions in parallel reaction monitoring (PRM) mode with observation of m/z 804.5580 > 577.4056 for lekethromycin and 777.5471 > 619.4522 for gamithromycin (internal standard, IS). The linear range was 5–1000 ng/mL (r2 > 0.99), and the lower limit of quantification (LLOQ) was 5 ng/mL. The intra- and inter-day precision (expressed as relative standard deviation, RSD) values were ≤7.3% and ≤6.3%, respectively, and the accuracy was ≥90% ± 5.3%. The mean extraction recovery RSD valWeue was <5.1%. Matrix effects and dilution integrity RSD values were <5.6% and <3.2%, respectively. Lekethromycin was deemed stable under certain storage conditions. This fully validated method was effectively applied to study the pharmacokinetics of lekethromycin after a single intravenous administration of 5 mg/kg in rats. The main pharmacokinetic parameters were T1/2λz, CL_obs and VZ_obs were 32.33 ± 14.63 h, 0.58 ± 0.17 L/h/kg and 25.56 ± 7.93 L/kg, respectively.

scholarly journals Determination of Progestin Residues in Fish by UPLC-Q-TOF/MS Coupled with QuEChERS

2019 ◽  
Vol 2019 ◽  
pp. 1-6
Author(s):  
Chunxiu Gu ◽  
Yanling Cheng ◽  
Xin Zhen ◽  
Xiaoxuan Chen ◽  
Kaowen Zhou
Keyword(s):  
Ultra Performance Liquid Chromatography ◽  
Technical Support ◽  
Quantitative Detection ◽  
Quechers Method ◽  
Aquatic Products ◽  
Flight Mass Spectrometry ◽  
Relative Standard ◽  
Novel Method ◽  
Tof Ms

A novel method was developed for simultaneous determination of 10 progestin residues in fish by ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF/MS) combined with a modified quick, easy, cheap, effective, rugged, and safe (QuEChERS) method. The homogenized samples were dispersed by water, extracted with acetonitrile, and then purified by QuEChERS reagent. The concentrated analytes were detected by UPLC-Q-TOF/MS. High linearities (R2 > 0.995) and recoveries (85.71–117.08%) at three spiked levels (5, 10, and 20 ng/g) and low relative standard deviation values (<8.83%, n = 7) and limits of detection (0.23–0.66 ng/g) were obtained. This method is simple, rapid, reliable, sensitive, and efficient and can be used for monitoring of progestin residues in fish. This method provides a strong guarantee to deal with food emergencies for the laboratory, provides technical support for the screening and quantitative detection of progesterone in fish, and provides technical support for the food safety of aquatic products.

scholarly journals SIMULTANEOUS ANALYTICAL METHOD DEVELOPMENT OF 6-MERCAPTOPURINE AND 6-METHYLMERCAPTOPURINE IN DRIED BLOOD SPOT USING ULTRA PERFORMANCE LIQUID CHROMATOGRAPHY TANDEM MASS SPECTROMETRY

2017 ◽  
Vol 9 ◽  
pp. 168
Author(s):  
Marlina Ika ◽  
Rizka Andalusia ◽  
Supandi Supandi ◽  
Yahdiana Harahap
Keyword(s):  
Liquid Chromatography ◽  
Method Development ◽  
Matrix Effects ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Ultra Performance Liquid Chromatography ◽  
Dried Blood Spot ◽  
Mass Detection ◽  
Relative Standard ◽  
Blood Spot

Objective: 6-mercaptopurine (6-MP) is a chemotherapeutic agent in the antimetabolite class. It has to go through the metabolic pathway to form6-methyl MP (6-MMP). This study aimed to obtain an optimum and validated method for the analysis of 6-MP and 6-MMP in dried blood spot (DBS)samples simultaneously and to evaluate the potential for future drug concentration monitoring in DBS samples.Methods: The quality control and calibration curves were made by spotting 40 μL blood on DBS paper and dried for 3 hrs. DBS papers were cut with adiameter of 8 mm and extracted with acetonitrile-methanol (1:3) containing internal standard 5-fluorouracil (5-FU). Separation was performed withwaters acquity ultra performance liquid chromatography BEH C18 column of 1.7 μm (2.1×100 mm) with a mobile phase consisting of 0.1% formicacid in water 0.1% formic acid in acetonitrile with gradient elution and a flow rate of 0.2 mL/minute. Mass detection was performed using WatersXevo TQD with positive electrospray ionization (ESI) for 6-MP and 6-MMP and negative ESI for 5-FU in the multiple reaction monitoring mode.Results: The detection rates of 6-MP, 6-MMP, and 5-FU were 153.09>119.09, 167.17>126.03, and 129.09>42.05, respectively. This method was linearwith the range at 26-1000 ng/mL for 6-MP and 13-500 ng/mL for 6-MMP with consecutive r≥0.998 and ≥0.999, respectively. The % relative errorvalue and % relative standard deviation for accuracy and precision of intraday and interday were not more than 15% and not more than 20% at thelower limit of quantification concentration, respectively.Conclusions: This method fulfilled the requirements of selectivity, linearity, carry over, and matrix effects referring to the European Medicines Agencyguidelines.

scholarly journals A Metabolomic Strategy to Screen the Prototype Components and Metabolites ofShuang-Huang-Lian Injectionin Human Serum by Ultra Performance Liquid Chromatography Coupled with Quadrupole Time-of-Flight Mass Spectrometry

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Mingxing Guo ◽  
Baosheng Zhao ◽  
Haiyu Liu ◽  
Li Zhang ◽  
Long Peng ◽  
...  
Keyword(s):  
Human Serum ◽  
Human Body ◽  
Matrix Effects ◽  
Ultra Performance Liquid Chromatography ◽  
Acute Respiratory Tract Infection ◽  
Chemical Compositions ◽  
Drug Induced ◽  
Flight Mass Spectrometry ◽  
Chinese Patent ◽  
Metabolic Reactions

Shuang-huang-lian injection(SHLI) is a famous Chinese patent medicine, which has been wildly used in clinic to treat acute respiratory tract infection, pneumonia, influenza, and so forth. Despite the widespread clinical application, the prototype components and metabolites ofSHLIhave not been fully elucidated, especially in human body. To discover and screen the constituents or metabolites of Chinese medicine in biofluids tends to be more and more difficult due to the complexity of chemical compositions, metabolic reactions and matrix effects. In this work, a metabolomic strategy to comprehensively elucidate the prototype components and metabolites ofSHLIin human serum conducted by UPLC-Q-TOF/MS was developed. Orthogonal partial least squared discriminant analysis (OPLS-DA) was applied to distinguish the exogenous, namely, drug-induced constituents, from endogenous in human serum. In the S-plot, 35 drug-induced constituents were found, including 23 prototype compounds and 12 metabolites which indicated thatSHLIin human body mainly caused phase II metabolite reactions. It was concluded that the metabolomic strategy for identification of herbal constituents and metabolites in biological samples was successfully developed. This identification and structural elucidation of the chemical compounds provided essential data for further pharmacological and pharmacokinetics study ofSHLI.

scholarly journals Validation of a New Sensitive Method for the Detection and Quantification of R and S-Epimers of Ergot Alkaloids in Canadian Spring Wheat Utilizing Deuterated Lysergic Acid Diethylamide as an Internal Standard

Toxins ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 22
Author(s):  
Jensen Cherewyk ◽  
Taylor Grusie-Ogilvie ◽  
Barry Blakley ◽  
Ahmad Al-Dissi
Keyword(s):  
Spring Wheat ◽  
Matrix Effects ◽  
Limit Of Detection ◽  
Ergot Alkaloids ◽  
Internal Standard ◽  
Lysergic Acid ◽  
Lysergic Acid Diethylamide ◽  
Relative Standard ◽  
Validation Parameters ◽  
Sensitive Method

Ergot sclerotia effect cereal crops intended for consumption. Ergot alkaloids within ergot sclerotia are assessed to ensure contamination is below safety standards established for human and animal health. Ergot alkaloids exist in two configurations, the R and S-epimers. It is important to quantify both configurations. The objective of this study was to validate a new ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method for quantification of six R and six S-epimers of ergot alkaloids in hard red spring wheat utilizing deuterated lysergic acid diethylamide (LSD-D3) as an internal standard. Validation parameters such as linearity, limit of detection (LOD), limit of quantification (LOQ), matrix effects, recovery and precision were investigated. For the 12 epimers analyzed, low LOD and LOQ values were observed, allowing for the sensitive detection of ergot epimers. Matrix effects ranged between 101–113% in a representative wheat matrix. Recovery was 68.3–119.1% with an inter-day precision of <24% relative standard deviation (RSD). The validation parameters conform with previous studies and exhibit differences between the R and S-epimers which has been rarely documented. This new sensitive method allows for the use of a new internal standard and can be incorporated and applied to research or diagnostic laboratories.

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 The Evaluation of Toxicity Induced by Psoraleae Fructus in Rats Using Untargeted Metabonomic Method Based on UPLC-Q-TOF/MS

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Yanyan Xu ◽  
Yiwei Zhao ◽  
Jiabin Xie ◽  
Xue Sheng ◽  
Yubo Li ◽  
...  
Keyword(s):  
Metabolic Pathways ◽  
Acid Metabolism ◽  
Safety Evaluation ◽  
Rat Plasma ◽  
Leguminous Plant ◽  
Control Group ◽  
Kidney Toxicity ◽  
Flight Mass Spectrometry ◽  
Liver And Kidney ◽  
Tof Ms

Psoraleae Fructus is the dry and mature fruit of leguminous plant Psoralea corylifolia L., with the activity of warming kidney and enhancing yang, warming spleen, and other effects. However, large doses can cause liver and kidney toxicity. Therefore, it is necessary to evaluate the toxicity of Psoraleae Fructus systematically. Although traditional biochemical indicators and pathological tests have been used to evaluate the safety of drug, these methods lack sensitivity and specificity, so a fast and sensitive analytical method is urgently needed. In this study, an ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) method was used to analyze the metabolic profiles of rat plasma. The changes of metabolites in plasma samples were detected by partial least squares-discriminant analysis (PLS-DA). Compared with the control group, after 7 days of administration, the pathological sections showed liver and kidney toxicity, and the metabolic trend was changed. Finally, 13 potential biomarkers related to the toxicity of Psoraleae Fructus were screened. The metabolic pathways involved were glycerol phospholipids metabolism, amino acid metabolism, energy metabolism, and so forth. The discovery of these biomarkers laid a foundation for better explaining the hepatotoxicity and nephrotoxicity of Psoraleae Fructus and provided a guarantee for its safety evaluation.

scholarly journals Rapid Analysis of the Main Components of the Total Glycosides of Ranunculus japonicus by UPLC/Q-TOF-MS

2010 ◽  
Vol 5 (5) ◽  
pp. 1934578X1000500
Author(s):  
Wen Rui ◽  
Hongyuan Chen ◽  
Yuzhi Tan ◽  
Yanmei Zhong ◽  
Yifan Feng
Keyword(s):  
Relevant Literature ◽  
Ultra Performance Liquid Chromatography ◽  
Flavonoid Glycosides ◽  
Complex Samples ◽  
Flavonoid Aglycones ◽  
Flight Mass Spectrometry ◽  
Fragment Ions ◽  
Main Components ◽  
Acquity Uplc ◽  
Tof Ms

A rapid method for the analysis of the main components of the total glycosides of Ranunculus japonicus (TGOR) was developed using ultra-performance liquid chromatography with quadrupole-time-of-flight mass spectrometry (UPLC/Q-TOF-MS). The separation analysis was performed on a Waters Acquity UPLC system and the accurate mass of molecules and their fragment ions were determined by Q-TOF MS. Twenty compounds, including lactone glycosides, flavonoid glycosides and flavonoid aglycones, were identified and tentatively deduced on the basis of their elemental compositions, MS/MS data and relevant literature. The results demonstrated that lactone glycosides and flavonoids were the main constituents of TGOR. Furthermore, an effective and rapid pattern was established allowing for the comprehensive and systematic characterization of the complex samples.

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