Thermally induced solid-state transformation of cimetidine. A multi-spectroscopic/chemometrics determination of the kinetics of the process and structural elucidation of one of the products as a stable N3-enamino tautomer

Exposure of cimetidine (CIM) to dry heat (160–180 °C) afforded, upon cooling, a glassy solid containing new and hitherto unknown products. The kinetics of this process was studied by a second order chemometrics-assisted multi-spectroscopic approach. Proton and carbon-13 nuclear magnetic resonance (NMR), as well as ultraviolet and infrared spectroscopic data were jointly used, whereas multivariate curve resolution with alternating least squares (MCR-ALS) was employed as the chemometrics method to extract process information. It was established that drug degradation follows a first order kinetics.     

西咪替丁的应用进展

综述了近年来国内外报道的H2受体抗拮剂－西咪替丁应用于除治疗消化性溃疡以外的其他疾病的进展情况，以其为临床用药提供参考。     

裸玻碳电极伏安测定甲氰咪胍

提出了裸ＧＣＥ不需任何处理测定甲氰咪胍的方法，浓度在３×１０＾－７－６×１０＾－５ｇ／ｍＬ，范围内与峰电流呈线性关系，ＲＳＤ为２．２％，回收率为９６％－１０２％。该方法操作简便快速，大多数金属离子和多种有机生化物质不干扰测定，方法用于片剂和加标尿样中甲氰咪胍的测定与药典方法对照，获得满意结果，并对电极反应进行了初步探讨。     

Chemical and analytical characterization of related organic impurities in drugs

A system is proposed for the classification of related organic impurities in drugs and drug products including among others (separated and non-separated) intermediates, various kinds of by-products, among them products of different side reactions, epimeric/diastereomeric, enantiomeric impurities, impurities in natural products, and finally degradation products. Examples are taken mainly from the author's own experience and from among the named impurities in the European Pharmacopoeia with focus on impurities in hydrocortisone, prednisolone, enalapril maleate, lisinopril, ethynodiol diacetate, pipecuronium bromide, cimetidine, and ethynylsteroids. The methodological aspects of impurity profiling from the detection to the identification/structure elucidation and quantitative determination of impurities are briefly summarized.This paper is Part 23 in the series "Estimation of impurity profiles of drugs and related materials". For Part 22 see ref. [1].     

Ternary complexes of cimetidine and phenobarbital with Cu(II) in methanolic solution

The formation constants of the binary complexes Cu(CM)²⁺ and Cu(CM) ₂ ²⁺ as well as those of the ternary complexes Cu(CM)L ⁺ and Cu(CM)₂ L ⁺ (CM=Cimetidine=N-Cyano-N-methyl-N[(5-methyl-1H-imidazol-4-yl)methyltioethyl]-guanidine; HL=Phenobarbital=5-ethyl-5-phenyl-barbituric acid) have been determined in 0.1 and 1.0 mol dm^–3 NaClO₄ methanol solutions at 25±0.2°C. The values of logX, log _stat.., and logK confirm the stability of the ternary complexes.

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Ternäre Komplexe von Cimetidin und Phenobarbital mit Cu(II) in methanolischer Lösung

Zusammenfassung Die Stabilitätskonstanten der binären Komplexe Cu(CM)²⁺ und Cu(CM) ₂ ²⁺ sowie die der ternären Komplexe Cu(CM)L ⁺ und Cu(CM)₂ L ⁺ (CM=Cimetidin=N-Cyan-N-methyl-N-[(5-methyl-1H-imidazol-4-yl)methylthioethyl]-guanidin; HL=Phenobarbitalum=5-Ethyl-5-phenyl-barbitursäure) wurden in 0.1 und 1.0M Lösungen von NaClO₄ in Methanol bei 25±0.2°C bestimmt. Die Werte von logX, log _stat. und logK bestätigen die Stabilität der ternären Komplexe.

     

毛细管电泳电导法快速测定西米替叮的方法

建立了毛细管电泳电导法快速测定西米替叮的方法.利用非涂层弹性融硅石英毛细管(50cm×75μm)为分离通道,探讨了缓冲溶液的种类、pH值、浓度,分离电压,进样时间对分离检测的影响.结果表明,在最佳条件下:30mmol/LTris(Cit调节pH=8.0)为运行缓冲介质,分离电压为10kv,西米替叮在10分钟内能得到较好的检测.标准品溶液浓度在0.5-20mg/L范围内有良好的线性关系,回归方程为y=9.0923x 15.83,相关系数r=0.9984,回收率为98.8%.     

Determination of cimetidine in human plasma by use of coupled-flow injection, solid-phase extraction, and capillary zone electrophoresis

Summary An on-line flow injection-solid-phase extraction-capillary zone electrophoresis (FI-SPE-CZE) method has been developed for determination of cimetidine in human plasma. Sodium dodecylsulfate (SDS) was used as dynamic chemical modifier for elimination of capillary contamination by biological macromolecules. FI on-line preconcentration and cleaning of the analyte by means of a C₁₈ microcolumn was performed automatically and CZE separation was performed consecutively without interruption of the applied voltage and between-run-washing of the capillary. A detection limit of 8 μgL⁻¹ (3×σ) was achieved at a sample throughput of 12h⁻¹. The approach was successfully used for a pharmacokinetic study of cimetidine.     

西咪替丁治疗消化性溃疡与其它药物的合理应用

对西咪替丁治疗消化性溃疡与其它药物方面不良相互作用以及使用不当进行了分析，并且提出了合理应用之对策。     

复发性单纯疱疹病毒性角膜炎临床疗效观察

目的 观察甲氰咪胍辅治及预防复发性单纯疱疹病毒性角膜炎(HSK)的疗效．方法 患者给予甲氰咪胍(0．25％)滴眼，1滴／次，8次／d，甲氰咪胍400mg加入注射用生理盐水100mL静滴，1次／d；无环鸟苷眼药水滴眼，6次／d．治愈后甲氰咪胍(0．25％)眼药水滴眼，4次／d，每周连用3d．结果治疗HSK病人38例38眼，1周后总有效率为94％，无效2例，占5％；复发2例，占5％．所有病人均未见明显不良反应．结论 甲氰咪胍辅治及预防HSK是一种安全有效的治疗方法．     

西咪替丁与氯醌酸荷移反应的研究

研究了西咪替丁与氯醌酸的荷移反应。确定了形成电荷转移络合物的最佳反应条件。在丙酮介质中,电子给体西咪替丁与电子受体氯醌酸于室温下可形成1：1的荷移络合物,络合物的最大吸收波长为516.6nm;表观摩尔吸光系数ε=2.22×103L.mol-1.cm-1;线性范围为6.8—112.0μg/mL;相关系数r为0.9995;并对形成荷移络合物的反应机理进行了探讨,并应用拟定的方法对样品西咪替丁片剂进行了含量测定,回收率为99.44%—100.20%;RSD为1.3%。