A rapid and sensitive liquid chromatographyetandem mass spectrometry method was developed and validated for the quantification of cyclobenzaprine in dog plasma.After extracted with organic solvent,post-treatment sampl...A rapid and sensitive liquid chromatographyetandem mass spectrometry method was developed and validated for the quantification of cyclobenzaprine in dog plasma.After extracted with organic solvent,post-treatment samples were separated on an Agela C18 column interfaced with a triple quadrupole tandem mass spectrometer in positive electrospray ionization mode.Multiple reaction monitoring was performed using the transitions of m/z 276.2/216.1 and m/z 325.1/109.0 to quantify cyclobenzaprine and escitalopram(internal standard),respectively.The mobile phase consisted of acetonitrile:5 mM ammonium acetate:formic acid(90:10:0.01,v/v/v)at a flow rate of 0.3 ml/min.The total analysis time was 2.4 min.The method was linear over the concentration range of 0.0200e10.0 ng/ml.The intra-and inter-day precision was within 12.8%in terms of relative standard deviation(RSD%)and the accuracy within 5.6%in terms of relative error.This method was successfully applied in a pharmacokinetic study of extended-release cyclobenzaprine in dogs.展开更多
A simple,rapid and robust high-throughput assay for the quantitative analysis of irbesartan in plasma from two species using liquid chromatography tandem mass spectrometric method was developed and validated.Solid p...A simple,rapid and robust high-throughput assay for the quantitative analysis of irbesartan in plasma from two species using liquid chromatography tandem mass spectrometric method was developed and validated.Solid phase extraction was used and quantification was achieved using a positive electrospray ionization interface under multiple reactions monitoring condition.Complete validation(as per recent regulatory requirements)was done using human plasma.The same method was validated using dog plasma and the validation parameters met respective acceptance criteria.The method has shorter run time of 3 min.This will help in high throughput.The low aliquot volume in the method helped us to take enough sampling time points for better pharmacokinetic profiles.The calibration curve was shown to be linear from 12.1 to 6018.7 ng/ml in human plasma and 12.1 to 5987.2 ng/ml in dog plasma.This method was successfully applied to samples collected during bioavailability studies of irbesartan in humans and dogs.展开更多
Effective annotation of in vivo drug metabolites using liquid chromatography-mass spectrometry(LCeMS)remains a formidable challenge.Herein,a metabolic reaction-based molecular networking(MRMN)strategy is introduced,wh...Effective annotation of in vivo drug metabolites using liquid chromatography-mass spectrometry(LCeMS)remains a formidable challenge.Herein,a metabolic reaction-based molecular networking(MRMN)strategy is introduced,which enables the“one-pot”discovery of prototype drugs and their metabolites.MRMN constructs networks by matching metabolic reactions and evaluating MS^(2)spectral similarity,incorporating innovations and improvements in feature degradation of MS^(2)spectra,exclusion of endogenous interference,and recognition of redundant nodes.A minimum 75%correlation between structural similarity and MS^(2)similarity of neighboring metabolites was ensured,mitigating false negatives due to spectral feature degradation.At least 79%of nodes,49%of edges,and 97%of subnetworks were reduced by an exclusion strategy of endogenous ions compared to the Global Natural Products Social Molecular Networking(GNPS)platform.Furthermore,an approach of redundant ions identification was refined,achieving a 10%-40%recognition rate across different samples.The effectiveness ofMRMN was validated through a single compound,plant extract,and mixtures of multiple plant extracts.Notably,MRMN is freely accessible online at https://yaolab.network,broadening its applications.展开更多
文摘A rapid and sensitive liquid chromatographyetandem mass spectrometry method was developed and validated for the quantification of cyclobenzaprine in dog plasma.After extracted with organic solvent,post-treatment samples were separated on an Agela C18 column interfaced with a triple quadrupole tandem mass spectrometer in positive electrospray ionization mode.Multiple reaction monitoring was performed using the transitions of m/z 276.2/216.1 and m/z 325.1/109.0 to quantify cyclobenzaprine and escitalopram(internal standard),respectively.The mobile phase consisted of acetonitrile:5 mM ammonium acetate:formic acid(90:10:0.01,v/v/v)at a flow rate of 0.3 ml/min.The total analysis time was 2.4 min.The method was linear over the concentration range of 0.0200e10.0 ng/ml.The intra-and inter-day precision was within 12.8%in terms of relative standard deviation(RSD%)and the accuracy within 5.6%in terms of relative error.This method was successfully applied in a pharmacokinetic study of extended-release cyclobenzaprine in dogs.
基金The authors acknowledge Ranbaxy Laboratories Limited to supports this study.
文摘A simple,rapid and robust high-throughput assay for the quantitative analysis of irbesartan in plasma from two species using liquid chromatography tandem mass spectrometric method was developed and validated.Solid phase extraction was used and quantification was achieved using a positive electrospray ionization interface under multiple reactions monitoring condition.Complete validation(as per recent regulatory requirements)was done using human plasma.The same method was validated using dog plasma and the validation parameters met respective acceptance criteria.The method has shorter run time of 3 min.This will help in high throughput.The low aliquot volume in the method helped us to take enough sampling time points for better pharmacokinetic profiles.The calibration curve was shown to be linear from 12.1 to 6018.7 ng/ml in human plasma and 12.1 to 5987.2 ng/ml in dog plasma.This method was successfully applied to samples collected during bioavailability studies of irbesartan in humans and dogs.
基金was financially supported by the National Natural Science Foundation of China(U23A20500,82374011,82474050,82404818)the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(ZYYCXTU-D-202203,China)+6 种基金the Guangdong Basic and Applied Basic Research Foundation(2025A1515011795,2023A1515011144,2024A1515012714,2024A1515011699,China)the Guangzhou Basic and Applied Basic Research Foundation(2024A04J3398,China)the China Postdoctoral Science Foundation(2023M741395)the Postdoctoral Fellowship Program of CPSF(GZB20240274,China)the Natural Science Foundation of Guangxi(2025GXNSFBA069293,China)the Scientific Research Start-up Funding Project of Guangxi University(ZX01080033724006,China)supported by the Fundamental Research Funds for the Central Universities(China).
文摘Effective annotation of in vivo drug metabolites using liquid chromatography-mass spectrometry(LCeMS)remains a formidable challenge.Herein,a metabolic reaction-based molecular networking(MRMN)strategy is introduced,which enables the“one-pot”discovery of prototype drugs and their metabolites.MRMN constructs networks by matching metabolic reactions and evaluating MS^(2)spectral similarity,incorporating innovations and improvements in feature degradation of MS^(2)spectra,exclusion of endogenous interference,and recognition of redundant nodes.A minimum 75%correlation between structural similarity and MS^(2)similarity of neighboring metabolites was ensured,mitigating false negatives due to spectral feature degradation.At least 79%of nodes,49%of edges,and 97%of subnetworks were reduced by an exclusion strategy of endogenous ions compared to the Global Natural Products Social Molecular Networking(GNPS)platform.Furthermore,an approach of redundant ions identification was refined,achieving a 10%-40%recognition rate across different samples.The effectiveness ofMRMN was validated through a single compound,plant extract,and mixtures of multiple plant extracts.Notably,MRMN is freely accessible online at https://yaolab.network,broadening its applications.
