Establishment Of New Techniques And Methods For Pharmaceutical Analysis

With the development of drug analysis and research, traditional separation andanalysis techniques can not meet the requirement of study. Efficient techniques andmethods are desired for the modern science, for the purpose of avoiding interference ofcomplex matrices to instrumental analysis, concentrating trace analytes, and controllingdrug quality in a more appropriate way. In the present study, some new techniques andmethods were developed for the drug analysis and qulity control.1. Restricted-access materials based on non-ionic surfactant-coateddodecyl-functionalized magnetic nanoparticles were prepared and applied to extractsteroid hormones from environmental and biological samples. The magnetic nanoparticleswere synthesized by co-precipitation, and were functionalized with dodecyltriethoxysilane,giving dodecyl-grafted magnetic nanoparticles (C₁₂-Fe₃O₄). They were further modifiedwith different non-ionic surfactants by self-assembly adsorption. Several types ofnon-ionic surfactants, Tween-20,40,60and85and Span-40,60and80were investigatedas the coatings. Tween surfactants coated C₁₂-Fe₃O₄, named as TW-20（40,60,85）-C₁₂,exhibited good dispersibility in aqueous solution, which was a preferred character inextraction; besides,TW-20-C₁₂and TW-40-C₁₂showed good anti-interference ability andsatisfactory reproducibility when they were used as magnetic solid-phase extraction（MSPE） sorbents. The factors that may influence the extraction, including the amount ofmagnetic nanoparticles, extraction and desorption time, the amount of salt addition, thetype and volume of desorption solvent, the volume of methanol addition and pH of samplesolution were investigated in detail. High performance liquid chromatography–UVdetection was employed for analysis of target analytes （steroid hormone compounds）.Thedeveloped method was successfully used for the determination of the target analytes inenvironmental and urine samples. Both tested materials afforded good recovery,satisfactory reproducibility and low limits of detection for environmental samples, whichindicates that the materials possessed anti-interference ability. However, compared toTW-40-C₁₂, TW-20-C₁₂nanoparticles provided better recovery in relatively complexbiological samples, which may indicate that the latter one is more appreciated in complexsamples. 2. Nonaqueous capillary electrophoretic separation of imatinib mesylate （IM） andrelated substances, N-（5-amino-2-methylphenyl）-4-（3-pyridyl）-2-pyrimidinamine （PYA）,N-（4-methyl-3-（4-（pyridin-3-yl）pyrimidin-2-ylamino）phenyl）-4-（（piperazin-1-yl）methyl）b-enzamide （NDI） and4-chloromethyl-N-（4-methyl-3-（（4-（pyridin-3-yl）pyrimidin-2-yl）amino）phenyl）benzamide（CPB） was developed. The influential factors affecting separation, including type andconcentration of the electrolyte, applied voltage and buffer modifier were investigated.Baseline separation of the studied analytes was obtained using a buffer of50mM Tris and50mM methanesulfonic acid in methanol at a apparent pH （pH*） of1.65. To enhance thesensitivity, large-volume sample stacking was employed for online concentration. Thestrongest analytical signal with a suitable separation was achieved when the injection timewas100s. The linearity ranges of PYA and NDI were0.100–2.500μg mL^-1,and that ofCPB was0.125–2.500μg mL^-1, with good coefficients （r2>0.9948）. The relative standarddeviations of intra-and interday were satisfactory. Under the optimized conditions, sevenbatches of the synthesized samples were analyzed and CPB was detected in two batches.Owing to its simplicity, effectiveness, and low price, the developed method is promisingfor quality control of IM.