Study On New Derivatization Method Of Gas Chromatography-mass Spectrometry And Application In Pharmaceutical Analysis

Part? Analysis of four antidepressants in plasma and urine by gas selective derivatizationObjective:To establish a novel sensitive and selective method for analysis four antidepressants:fluoxetine(Flu),nortriptyline(Nor),maprotiline(Map),and paroxetine(Paro)in plasma and urine by derivatization combined with gas chromatography-mass spectrometry(GC-MS).Methods:Antidepressants with secondary amines can react with sodium nitrite under acidic conditions to form corresponding N-nitrosamine.The conditions affecting derivative reactions and extraction of derivatives were optimized,including the amount of hydrochloric acid,the amount of sodium nitrite,reaction temperature,reaction time,extraction reagents and extraction time.The derivatives were extracted by dichloromethane and determined by gas chromatography-mass spectrometer.Results:Under the optimal conditions,the limit of detections(LODs)and the limit of quantitations(LOQs)of four antidepressants(Flu,Nor,Map,and Paro)were in the range of 0.04-1.38 ng/m L and 0.14-4.62 ng/m L,respectively.Low,medium,and high concentrations of antidepressants were added in plasma and urine samples,spiked recovery ranged from85.88%-110.34%for plasma and 80.64%-113.07%for urine,respectively.The method has good accuracy and precision.Conclusions:A novel high-sensitivity and high-selectivity GC-MS combined with derivatization approach for the detection of Flu,Nor,Map,and Paro in plasma and urine was established.Part? Determination of higenamine in multi-matrix by gas derivatization technologyObjective:To establish a gas chromatography-mass spectrometry(GC-MS)method,based on acylation derivatization,for determination of higenamine(HG)in various matrix samples(biological samples,different forms of Chinese patent medicine,Chinese herbal medicine),and to apply it successfully for screening medicines and foods for athletes,while providing useful anti-doping information.Methods:The experiment investigated the pretreatment methods of different matrix samples,then the pretreated samples were purified and concentrated with PEP-2 SPE column,and followed by the acylation derivatization of higenamine by heptafluorobutyric anhydride.Results:Under optimal conditions,the linearity of HG in the range of5-200 ng/m L was acceptable(R~2>0.999),and the limit of detection(LOD)and limit of quantitation(LOQ)for higenamine were 1.52 ng/m L and 5 ng/m L,respectively.Low,medium,and high concentrations(25,100 and 160 ng/m L)of HG were added to plasma,urine,different forms of Chinese patent medicine(oral liquid,capsule,watered bolus,honeyed bolus)and Chinese herbal medicine samples,with recovery ranging from 82.70%to 109.80%,intra-day and inter-day precisions were both less than 3.39%.Conclusions:In this study,a gas chromatography-mass spectrometry combined with derivatization technology method was developed to determine the content of the higenamine in a variety of matrix samples(biological samples,various formulations of Chinese patent medicines and Chinese herbal medicines).