Mass Spectrometry Was Used To Identify The Chiral Drugs Of Landiolol Hydrochloride And Glimepiride

Chirality is intrinsic property in the nature,and the pharmacological activity of a drug is closely related to the steric structure effect including the configuration of the drug.The stereo configuration of a drug influences the specificity,selectivity,and pharmacological activity by its combination with the receptors.With the fast-growing market of chiral drugs recent decades,control of stereoisomer impurities in chiral drugs is become more and more crucial,because the stereoisomer impurities usually have no therapeutic effects or even present drug side effects.The classical analysis methods of the chiral drugs are widespread applied,including polarimetric method,circular dichroism spectroscopy method,nuclear magnetic resonance?NMR?,X-ray diffraction experiment method and chromatography.However,these methods have been limited by some drawbacks,such as tedious analysis process,low sensitivity,large sample amount,unsatisfactory selectivity and high cost.It is necessary to develop rapid,simple and sensitive technology to achieve qualitative and quantitative determination.Mass spectrometry is an acknowledged analytical technology with the advantage of high sensitivity,quick and trace analysis;tandem mass spectrometry provides much information of the structure.By the development of collision-induced dissociation?CID?,it is possible to achieve the chiral recognition by comparing the competitive fragment ions of the chiral precursor ions.Chiral recognition by MS is widely applied for small molecular,like chiral amino acids and their analogue.However,this method applied into chiral drugs were rarely reported therefore we put forward the study as following:1,Recognition of Landiolol hydrochloride and its stereoisomer recognition research.Two chiral chloride probes were used to differentiate landiolol hydrochloride by mass spectrometry.Two chiral chloride probe reagents,N-?p-Tosyl?-L-phenylalaninyl chloride and?-?-Camphanic acid chloride,were chosen to react with landiolol hydrochloride and its stereoisomers to form covalent bonding derivatives,which enlarged the difference of stereo structure between landiolol and its stereoisomers.Tandem mass spectrometer were performed,and fragment from derivative products prefer to losing water to form fragment ions m/z 793?m/z 672.The relative abundance of ions m/z 793?m/z 672 were quite different in each isomers.The fragment ions m/z 603 from?-?-Camphanic acid chloride derivative products showed distinction relative abundance because of the difference stability of each stereoisomers,which was gave rise to the enlarged difference of stereo structure between landiolol and its stereoisomers.By comparing the different relative abundance ratio of analyte and each stereoisomer in MS/MS spectrums,we can realize recognization landiolol hydrochloride and its stereoisomers.Accurate masses of precursor and fragment ions were confirmed on an IT-TOF mass spectrometer.This method by using ion-trap mass spectrometry can rapidly and simply differentiate the landiolol hydrochloride and its stereoisomers.This work can contribute to differentiation and discrimination landiolol hydrochloride and its stereoisomers.2,A simple and rapid identification method of Glimepiride and its cis-isomer was established for the first time.The collision-induced dissociation?CID?mass spectrometry method was used in this study.And results implied that tandem mass spectrometry is a potential approach in stereochemical analysis.The fragments from precursor ions presented quite difference between Glimepiride and its cis-isomer.By comparing ratios of the competing fragmentation,the breakdown curves,which were confirmed through the method of energy-resolved mass spectrometry?ERMS?,were built to provide information on fragmentation.The RIsomer values,which evaluate the ability of the stereometrics recognition,were investigated at different collision energy.The transition metal ions often induce characteristic fragment pathway.After screening the transition metal ions,the zinc ion was selected as an induced reagent to amplify the recognition degree,and much higher R_Isomer values were observed by experiments.The quantitative determination of Glimepiride was performed by using MS/MS.Aiming at the recognition of stereoisomers,the methodology shows huge potential of extended application to a large number of chiral drugs and their impurity.