Improving analytical throughput is the focus of many quantitative workflows being developed for early drug discovery.For drug candidate screening,it is common practice to use ultra-high performance liquid chromatograp...Improving analytical throughput is the focus of many quantitative workflows being developed for early drug discovery.For drug candidate screening,it is common practice to use ultra-high performance liquid chromatography(U-HPLC)coupled with triple quadrupole mass spectrometry.This approach certainly results in short analytical run time;however,in assessing the true throughput,all aspects of the workflow needs to be considered,including instrument optimization and the necessity to re-run samples when information is missed.Here we describe a high-throughput metabolic stability assay with a simplified instrument set-up which significantly improves the overall assay efficiency.In addition,as the data is acquired in a non-biased manner,high information content of both the parent compound and metabolites is gathered at the same time to facilitate the decision of which compounds to proceed through the drug discovery pipeline.展开更多
In this paper,we report the construction of two accurate mass databases and the development of a combination detection method that simultaneously screens for 733 pesticide and chemical contaminant multi-residues via h...In this paper,we report the construction of two accurate mass databases and the development of a combination detection method that simultaneously screens for 733 pesticide and chemical contaminant multi-residues via high-throughput liquid chromatography(LC)-and gas chromatography(GC)-quadru pole-time-of-flight mass spectrometry(Q-TOFMS).This work demonstrates that electronic mass spectral standards may replace chemical-source standard materials as references through one sample preparation and the combination of GC/LC-Q-TOFMS screening.This cutting-edge technique has also replaced multiresidue determination using targeted detection with non-targeted screening.The pesticide residue types,sensitivity,recovery,and reproducibility of this combination technique are evaluated in eight fruit and vegetable matrices.This technique shows three advantages:①In comparison with the discovery capability of a single technique,the combination technique shows an improvement of 51.1%(GC-QTOFMS)and 39.6%(LC-Q-TOFMS),respectively;②the combination technique can satisfy a screening limit lower than 10μg·kg^-1 and meet the requirements of“uniform standards,”although some of the pesticide residues could be optimized to further improve screening sensitivity;③over 488 pesticides with recoveries between 60%-120%and relative standard deviation(RSD)<20%at a spiked level of 10μg·kg^-1 were detected with the combination technique in eight different matrices.From 2012 to 2017,this combination technique was applied in an investigation to screen pesticide residues from 1384 sampling locations for 38138 batched samples covering 18 categories and 134 types of fruits and vegetables obtained from across the mainland of China.After statistical analysis,533 pesticides in 115891 determinations were detected,and the regularity of pesticides in the fruits and vegetables sold on the Chinese market was shown.展开更多
A more comprehensive calibration involving m/z and peak shape has been developed to attain the high spectral accuracy necessary to achieve unique elemental composition determination. This approach can be applied for f...A more comprehensive calibration involving m/z and peak shape has been developed to attain the high spectral accuracy necessary to achieve unique elemental composition determination. This approach can be applied for formula determination at much lower resolution such as single or triple quadrupole mass spectrometers.展开更多
文摘Improving analytical throughput is the focus of many quantitative workflows being developed for early drug discovery.For drug candidate screening,it is common practice to use ultra-high performance liquid chromatography(U-HPLC)coupled with triple quadrupole mass spectrometry.This approach certainly results in short analytical run time;however,in assessing the true throughput,all aspects of the workflow needs to be considered,including instrument optimization and the necessity to re-run samples when information is missed.Here we describe a high-throughput metabolic stability assay with a simplified instrument set-up which significantly improves the overall assay efficiency.In addition,as the data is acquired in a non-biased manner,high information content of both the parent compound and metabolites is gathered at the same time to facilitate the decision of which compounds to proceed through the drug discovery pipeline.
基金financial support of the National Key Technology Research and Development Program(2012BAD29B01)the Key Basic Research Program(2015FY111200)of the Ministry of Science and Technology,China.
文摘In this paper,we report the construction of two accurate mass databases and the development of a combination detection method that simultaneously screens for 733 pesticide and chemical contaminant multi-residues via high-throughput liquid chromatography(LC)-and gas chromatography(GC)-quadru pole-time-of-flight mass spectrometry(Q-TOFMS).This work demonstrates that electronic mass spectral standards may replace chemical-source standard materials as references through one sample preparation and the combination of GC/LC-Q-TOFMS screening.This cutting-edge technique has also replaced multiresidue determination using targeted detection with non-targeted screening.The pesticide residue types,sensitivity,recovery,and reproducibility of this combination technique are evaluated in eight fruit and vegetable matrices.This technique shows three advantages:①In comparison with the discovery capability of a single technique,the combination technique shows an improvement of 51.1%(GC-QTOFMS)and 39.6%(LC-Q-TOFMS),respectively;②the combination technique can satisfy a screening limit lower than 10μg·kg^-1 and meet the requirements of“uniform standards,”although some of the pesticide residues could be optimized to further improve screening sensitivity;③over 488 pesticides with recoveries between 60%-120%and relative standard deviation(RSD)<20%at a spiked level of 10μg·kg^-1 were detected with the combination technique in eight different matrices.From 2012 to 2017,this combination technique was applied in an investigation to screen pesticide residues from 1384 sampling locations for 38138 batched samples covering 18 categories and 134 types of fruits and vegetables obtained from across the mainland of China.After statistical analysis,533 pesticides in 115891 determinations were detected,and the regularity of pesticides in the fruits and vegetables sold on the Chinese market was shown.
文摘A more comprehensive calibration involving m/z and peak shape has been developed to attain the high spectral accuracy necessary to achieve unique elemental composition determination. This approach can be applied for formula determination at much lower resolution such as single or triple quadrupole mass spectrometers.
