盐酸曲马多离子选择性电极的研制与应用

介绍了盐酸曲马多离子选择性电极的制备,特性以及在药物分析方面的应用。综合考虑活性物质的含量和增塑剂种类及含量的影响,选择了以盐酸曲马多—四苯硼钠缔合物为活性物质,以DOP为增塑剂的电极体系。该电极在5×10-5～1×10-2mol/L范围内表现能斯特响应,斜率为57.1mV/pC,检测下限为1×10-5mol/L。电极对多种异质离子表现良好的选择性。运用电位法测定药物中的盐酸曲马多,回收率为94.9%～106.0%。     

Application of Adsorptive Stripping Voltammetry for the Nano‐Level Detection of Tramadol in Biological Fluids and Tablets Using Fast Fourier Transform Continuous Cyclic Voltammetry at an Au Microelectrode in a Flowing System

Abstract

A novel adsorptive fast Fourier transform cyclic voltammetry (AFFTCV) technique for the fast determination of tramadol in flow‐injection systems has been introduced in this work. The potential waveform, consisting of the potential steps for cleaning, stripping, and potential ramp, was continuously applied on an Au disk microelectrode (with a 12.5 µm in radius). The proposed detection method has some advantages, the greatest of which are as follows: first, it is no more necessary to remove oxygen from the analyte solution and second, it is a very fast and appropriate technique for determination of the drug compound in a wide variety of chromatographic analysis methods. The influences of pH of eluent, accumulation potential, sweep rate, and accumulation time on the determination of the tramadol were considered. The method was linear over the concentration range of 1.5–900,000 pg/ml (r=0.9968) with a limit of detection and quantitation 0.32 and 1.5 pg/ml, respectively. The method has the requisite accuracy, sensitivity, precision, and selectivity to assay tramadol in tablets and in biological fluids.     

Tramadol Release from a Delivery System Based on Alginate‐Chitosan Microcapsules

Alginate‐chitosan microcapsules to control the release of Tramadol‐HCl were prepared using two different methods. In the two‐stage procedure (Variant I) alginate was first pumped into a CaCl₂/NaCl solution and then transferred into a chitosan solution. In the one‐stage procedure (Variant II) alginate was directly pumped into a chitosan/CaCl₂ solution, and different behavior could be noted in each case. The microcapsules were spherical in both variants and they swelled to a greater extent in a basic medium as compared to an acid one. The drug release profile of Tramadol from microcapsules in simulated gastric fluid and simulated intestinal fluid was also studied. The maximum release of Tramadol at 24 h was 64% and 86% for Variant I and II, respectively, in simulated intestinal fluid. Release was adjusted using the power law of the semi‐empirical Peppas equation in order to gain information about the release mechanism. In both cases the values of the exponent were found to be between 0.53 and 0.84 for swellable microcapsules in simulated gastric and intestinal fluids, respectively, indicating anomalous drug transport for both variants. The good results obtained with alginate‐chitosan microcapsules are comparable to those of the best products so far described in the scientific bibliography and in addition, chitosan is useful in pharmacy.

Surface morphology of Tramadol‐loaded microcapsule.     

盐酸曲马多药物树脂制备技术的研究

采用静态法和动态法两种工艺制备盐酸曲马多药物树脂，并对制备过程中体系温度、反应时间、药物溶液浓度、溶液流速等影响因素进行了研究；以正交设计对工艺进行优化。     

A stability-indicating HPLC method for the determination of benzalkonium chloride in 0.5% tramadol ophthalmic solution

Summary A high-performance liquid chromatographic procedure employing ultraviolet detection for the analysis of benzalkonium chloride in 0.5% Tramadol ophthalmic solution is reported. The method requires minimal sample pretreatment and is sensitive, accurate, and reproducible. The peak area versus BAK concentration is linear over the range of 50–150% of its label claim of 0.05 mg/mL. The mean absolute recovery of BAK using the described method is 100.2±1.2%, (mean ±SD, n=10). A stress study with heat, acid, base and UV radiation indicates that the method is stabilityindicating with no interference from drug or degradation products.     

Stability evaluation of tramadol enantiomers using a chiral stability-indicating capillary electrophoresis method and its application to pharmaceutical analysis

In this study, a chiral stability-indicating CE assay was developed for the stability evaluation of tramadol (TR) enantiomers in commercial tablets using maltodextrin as chiral selector. To investigate the stability-indicating power of the analytical method as well as stability evaluation of TR enantiomers, active pharmaceutical ingredient and TR tablets were subjected to photolysis, heat, oxidation and hydrolysis to conduct stress testing. Best separation for the TR enantiomers was achieved on an uncoated fused-silica capillary at 20 °C using borate buffer (50 mM, pH 10.2) containing 10% m/v maltodextrin. All determinations were performed by a UV detector at 214 nm. A constant voltage of 20 kV was applied to obtain the separation. The range of quantitation for both enantiomers was 5-100 μg/mL (R>0.996). Intra- and inter-day RSD (n=6) were less than 10%. The percent relevant errors were obtained to be less than 4.0 for both enantiomers. The limits of quantitation and detection for both enantiomers were 5 and 1.5 μg/mL, respectively. Degradation products resulting from the stress studies were the same for both enantiomers and did not interfere with the detection of the enantiomers.     

FTIR和Raman用于盐酸曲马多的结构分析

采用AVATAR 360型傅里叶变换红外光谱仪和RM-1000型激光共聚焦拉曼光谱仪测定盐酸曲马多的红外光谱和拉曼光谱。拉曼光谱和红外光谱中均显示出了盐酸曲马多的特征峰,都能够用于其结构鉴别。采用红外、拉曼光谱这两种方法互相印证,互相补充,可增强鉴定的准确性、可靠性。     

Monodispersed Gold Nanoparticles Decorated Carbon Nanotubes as an Enhanced Sensing Platform for Nanomolar Detection of Tramadol

A promising composite‐modified glassy carbon electrode is fabricated by electrodeposition of mono‐dispersed gold nanoparticles onto carbon nanotubes (AuNPs/CNTs/GCE). The electroanalysis of Tramadol (TRA) was achieved by different electrochemical techniques. The effect of different parameters including pH, concentration and potential scan on the oxidation current signal of TRA was investigated. Large excess of ascorbic acid (AA) and uric acid (UA) with a maximum molar ratio of 1/1000 and 1/100, respectively, did not interfere with the response of TRA. The detection limit with high sensitivity is 68 nM. TRA was successfully determined in pharmaceutical dosage forms, without any pretreatment of the samples.     

凝胶醌氢醌PVC涂膜曲马多选择电极的研制

研制了一种新型PVC涂膜曲马多选择电极,该电极以凝胶醌氢醌电极为内参比电极,外涂含曲马多-四苯硼离子缔合物的PVC膜构建而成。其Nernst响应范围为4.0×10-5~1.0×10-2mol·L-1,斜率为57.4mV/pc(25℃),检出限为1.9×10-5mol·L-1,适用的pH范围为2~8。电极性能稳定,用于片剂中盐酸曲马多含量测定,回收率为96%~102%,结果与中国药典法一致。     

流动注射化学发光法测定盐酸曲马多

基于盐酸曲马多对酸性介质中高锰酸钾与亚硫酸钠间弱化学发光反应的显著增强作用,建立了一种流动注射化学发光法测定曲马多的新方法.并用荧光、紫外和化学发光光谱探讨了曲马多对这一体系增敏作用的机理.在优化的实验条件下,化学发光强度与曲马多的浓度在0.04～4.0 μg/mL内呈线性关系,相关系数为0.9995,检出限为0.01μg/mL.平行测定曲马多11次的相对标准偏差为2.1%.用本法对盐酸曲马多注射液中曲马多进行了测定,结果满意.