聚[碳酸(亚丁酯-co-ε-己内酯)酯]的制备及其载药微球性能的研究

采用阴离子配位聚合方法, 合成了二氧化碳、1,2-环氧丁烷与ε-己内酯的三元共聚物: 聚[碳酸(亚丁酯-co-ε-己内酯)酯](PBCL). 并采用复相乳液(W/O/W)溶剂挥发法制备了包裹抗菌药物甲磺酸帕珠沙星的可降解微球. 对聚合物进行了FTIR, ¹H NMR, ¹³C NMR, DSC, TGA和WAXD等表征, 以及降解性能和载药微球特性的研究. 结果表明, PBCL热稳定性及降解性能优于聚碳酸亚丁酯(PBC). 所得PBCL微球球形规整、表面光滑. 大部分微球粒径在0.5～1 μm的范围内, 载药量和包封率分别达到38.21%和87.9%. 微球的体外释药性能研究在pH 7.4的磷酸缓冲溶液中进行, 释放21 d后, PBCL微球的累积释药量为84.74%, PBC微球的释药量仅为17.29%. 药物的体外释放行为符合Higuchi方程. PBCL载药微球具有长效缓释作用.     

液相色谱-串联质谱法测定水产品中麻醉剂MS-222残留

建立了液相色谱-串联质谱法测定水产品中麻醉剂3-氨基苯甲酸乙酯甲基磺酸盐(MS-222)残留量的方法。提取液为50%的甲醇及乙酸-乙酸钠缓冲溶液,提取液经C18固相萃取柱净化处理后用液相色谱-串联质谱仪进行测定,外标法定量。流动相为0.5%的甲酸溶液和乙腈(V:V=60:40),流速为0.2 mL/min。该方法的线性范围为0.001～1.0 mg/L,相关系数大于0.999,检出限为1μg/kg,定量限为2μg/kg。加标回收率可以达到80%～110%。     

甲磺酸帕珠沙星的热分解机理及动力学

采用热重(TG)和差示扫描量热(DSC)法测定了甲磺酸帕珠沙星(PZFX)在氮气氛和空气氛中的热分解过程,测定了PZFX及其在热分解过程中不同阶段残余物的红外光谱,运用量子化学GAMESS软件计算了PZFX分子的键级,推断了PZFX的热分解机理.结果表明PZFX的热分解过程的起始步骤是甲磺酸的分解.采用Ozawa方法计...     

β-环糊精和磺化杯[4]芳烃修饰银纳米粒对甲磺酸帕珠沙星的比色检测

报道了β-环糊精和磺化杯[4]芳烃修饰银纳米粒的制备、表征及其作为甲磺酸帕珠沙星的比色探针的应用。结果表明,两种化学修饰银纳米粒对甲磺酸帕珠沙星都能较好地识别,对甲磺酸帕珠沙星的最低检出浓度可达1.0×10-5mol/L。     

A method for quantifying the unstable and highly polar drug nafamostat mesilate in human plasma with optimized solid-phase extraction and ESI-MS detection: more accurate evaluation for pharmacokinetic study

An advanced quantification method was developed with solid-phase extraction (SPE) and mass spectrometry (MS) determination for nafamostat, an unstable and highly polar drug, in human plasma. For unstable drugs with an ester group, the main analytical challenge is how to avoid the ester hydrolysis, and strong acid or alkaline conditions should be excluded during sample preparation. Considering that, we developed a relatively mild method with SPE for sample preparation without strong acid and alkaline treatment, which was optimized with different pHs and salt concentrations in phosphate-buffered saline treatment. The results indicated that pH 5 gave the most efficient extraction and 0.1 M salt concentration enhanced the extraction the most, with a minor effect on MS monitoring. The extraction method effectively avoided drug hydrolysis and achieved good drug enrichment over 82.2%. The linear range of quantification was 1.25–160 ng mL⁻¹. The stability of the drug in sample treatment was fully validated according to the sample processing procedure, including the stability in fresh blood, mobile phase, plasma and acidic methanol, and the results indicated that the drug remained stable during the whole sample preparation. Compared with a previous isotope-labeling method, more accurate and specific quantification of plasma concentration was achieved with liquid chromatography–electrospray ionization MS determination. With use of our method, nafamostat mesilate pharmacokinetics in 30 Chinese healthy volunteers was investigated with three doses via intravenous-drip infusion. The pharmacokinetic parameters were also estimated and compared with those of Japanese volunteers (slightly lower plasma concentration and longer terminal elimination half-life for Chinese volunteers). The difference in the pharmacokinetics may be ascribed to the quantification method, because previous isotope labeling may have overestimated the parent drug.     

Interaction study between pefloxacin mesilate and some diluents using DSC supported with isothermal method

The present investigation was carried out to screen compatibility of some diluents with pefloxacin mesilate using differential scanning calorimetry (DSC), isothermal stability studies, along with stability studies in liquid state and to assign relative ranking to diluents. Compatibility was predicted with MCC101, MCC102, DCP anhydrous, Emcompress, while melting endotherm of drug was lost in admixtures of dextrose anhydrous, Pearlitol, Lactopress spray dried, Lactochem fine powder and Lycatab indicating possibility of interaction. Enthalpy changes were used for relative ranking of diluents.     

高效毛细管电泳法测定人血及尿样中甲磺酸帕珠沙星

采用高效毛细管电泳法测定甲磺酸帕珠沙星在人血及尿样中的含量。实验用未涂层弹性石英毛细管柱,规格是39 cm×50μm(i.d.),其有效长度为28.5 cm。pH 6.0的磷酸盐缓冲溶液(75 mmol/L)作为运行缓冲液,氧氟沙星为内标,在10 kV高压下进样12 s,分离电压选择20 kV,在波长为247 nm的条件下,可有效分离甲磺酸帕珠沙星与氧氟沙星。甲磺酸帕珠沙星在10~700μg/L质量浓度范围内线性良好(r=0.999 6),检出限为5.0μg/L。此方法简便、准确、重复性好。     

Application of XRD-DSC system to the optimization of manufacturing process for the freeze-dried pharmaceuticals

We have developed the vacuum dryer attached XRD-DSC system and monitored manufacturing process of freeze-dried pharmaceutical product. The aim of this study is to apply the XRD-DSC system for the preformulation of freeze-dried injections. Gabexate mesilate was used as a model drug. Drug solution was frozen then heated to annealing temperature according to the process-controlling program. The XRD-DSC analyses were performed to monitor the crystallized spicies and their crystallinity of sample. When the solution was cooled slowly, peaks of gabexate mesilate and mannitol polymorph had been already observed during the cooling process while those crystallinity were low at fast cooling rate. As the drying underwent, intensity of ice peaks were getting weaker. At the cooling rate of 0.1°C min^–1, the XRD profile of final product was revealed that the characteristic peaks of gabexate mesilate, mannitol δ-form and β-form were appeared. When the cooling rate was increased, the crystallinity of final products was decreased. From these results, it was confirmed that the XRD profiles during freeze-drying process significantly related to the final freeze-dried product. It is obvious that monitoring by XRD-DSC system is a quite effective way to simulate the manufacturing process and to optimize the qualified product.     

甲磺酸卡莫他特的合成

甲磺酸卡莫他特是口服有效的丝氨酸蛋白酶抑制剂。文献的合成方法有二种。其中一种为化合物3先与SOCl2反应成酰氯后,再与化合物2反应。