HPLC法测定健康人血浆中莫雷西嗪浓度及其药代动力学研究

目的建立测定人血浆中莫雷西嗪(抗心律失常药)浓度的高效液相色谱法。方法色谱柱HypersilODS(150mm×4.6mm,5μm);流动相:甲醇-水-三乙胺(70∶30∶0.4,pH6.8);检测波长:268nm;氯氮平作为内标,用HPLC法测定人血浆中的莫雷西嗪浓度。结果莫雷西嗪浓度线性范围为0.04～4μg.mL-1,回归方程Y=11.42X 1.44,γ=0.9992;回收率>85%,日内和日间RSD均<15%。结论本方法简便、快速、准确,适用于莫雷西嗪药代动力学研究及血药浓度监测。     

Rate-dependent anisotropic conduction property in the epicardial border zone of canine myocardial infarcts and its modification by moricizine

Summary We evaluated anisotropic conduction properties, different conduction velocities depending on fiber orientation, in normal and infarcted myocardium and the effects of moricizine on anisotropic conduction. Various cycle lengths of stimulation were applied to 15 mongrel dogs, and epicardial mapping was performed using a 96-channel mapping electrode. Moricizine was then administered to seven dogs and the same procedure was performed. Conduction velocities were calculated from these maps. Programmed electrical stimulations were performed before and after moricizine administration to induce ventricular arrhythmias. Before moricizine administration, a rate-dependent decrease in longitudinal conduction velocity was observed in the infarcted zone. Moricizine suppressed longitudinal conduction in the normal zone significantly at 300 msec pacing, but not at slower rates. Moricizine at a dose of 4 mg/kg, on the other hand, suppressed longitudinal conduction in the infarcted zone significantly at all pacing cycle lengths. The effect of moricizine on transverse conduction was inconsistent. In three dogs, sustained ventricular tachycardia (VT) was induced either before or after moricizine administration. The mean cycle length of sustained VT was prolonged from 202 msec to 291 msec after 4 mg/kg of moricizine. Thus, the changes in cycle length of ventricular tachycardia observed were most likely the result of slowing of conduction velocity, especially in the longitudinal direction, in the infarcted myocardium. We conclude that the electrophysiologic nature of the subacute ischemic model was modified by moricizine, leading to depression of the conduction velocity of longitudinal conduction and the inducibility of ventircular arrhythmias.     

药物敏感场效应晶体管测定丁氯喘片剂含量

将离子敏感场效应晶体管与药物敏感膜相结合，制成药物敏感效应晶体管传感器，测定丁氯喘片剂含量。以磷钨酸为电活性物质，制成PVC膜，对丁氯喘的线性响应范围为100～0．03mmol／L，斜率为59mV，适宜pH范围为3．0～8．0，检测下限为0．01mmol／L。     

基于总处方量的不良反应报告分析对盐酸伐地那非安全性评估研究

目的：基于盐酸伐地那非（艾力达）上市以来总处方量的不良反应报告分析,评估其安全性,旨在对临床规范用药提供有益借鉴。方法：查阅WHO药品不良反应数据库,检索并分析比较药品不良反应报告。结果：药品不良反应报告主要集中在心血管等系统。各个系统不良反应表现形式各异,但都比较轻微,基于总处方量来讲,不良反应报告率极低。严重不良反应如心肌梗塞、异常勃起的报告率极少。结论：枸橼酸西地那非治疗勃起功能障碍的安全性比较高;应继续规范药物的临床应用,尽量减少死亡、异常勃起等严重不良反应的发生。     

ＨＰＬＣ法测定盐酸丁咯地尔注射液的含量与杂质

目的：对盐酸丁咯地尔注射液的质量进行分析测定。方法：采用甲醇－水－冰醋酸－三乙胺流动相体系的ＨＰＬＣ法。结果：盐酸丁咯地尔与有关物质间有良好分离。结论：所建立的ＨＰＬＣ方法稳定、简便准确。     

Moricizine-induced proarrhythmia

Moricizine is a Class I antiarrhythmic drug currently approved for the treatment of life-threatening ventricular arrhythmias. The drug has received significant attention because of its role in the Cardiac Arrhythmia Suppression Trial. Previous data suggested that the agent has a relatively low proarrhythmic potential. This may lead clinicians to use the drug empirically for less significant ventricular arrhythmias. We report a case of life-threatening late proarrhythmia caused by moricizine and comment on our experience with this agent. We feel that this drug has significant proarrhythmic potential and should not be used empirically to treat ventricular ectopy especially in patients with underlying structural heart disease.     

非水电位滴定法测定盐酸莫雷西嗪原料的含量

目的建立革除汞盐的非水电位滴定法测定盐酸莫雷西嗪原料的含量。方法建立以冰醋酸与醋酐（1：3）为溶剂的高氯酸非水电位滴定法测定盐酸莫雷西嗪原料的含量。结果与2005年版《中国药典（二部）》方法测定结果一致。结论该法操作简单,灵敏度高,准确可靠,重复性及稳定性良好,适于盐酸莫雷西嗪原料的含量测定。     

用高效液相色谱法测定莫雷西嗪及其代谢产物在血及尿中的浓度

应用高效液相色谱法测定人体血浆、尿液中莫雷西嗪及其亚砜、砜代谢产物的生物浓度，本法选用国产硅胶ＹＷＧ－Ｃ１８为固定要，甲醇、乙腈、水、三乙胺为流动相，检测波长２５４ｎｍ．采用离子对一步提取法提取样品，莫雷西嗪，莫雷西嗪亚砜和莫雷西嗪亚砜和莫西嗪的最低血浆检测浓度为３０、８、１０ｎｍ／ｇｍｌ，绝对回收率大于８５％。     

液质联用测定健康人血浆中莫雷西嗪浓度及其药代动力学研究

目的 建立液质联用法并测定人血浆中莫雷西嗪浓度。方法 色谱条件 为Kromasil C18(150 mm×4．6mm,5μm),流动相:乙腈-10mmol·L-1醋酸铵 缓冲液-冰醋酸(50:50:0．45);质谱条件为离子源大气压化学电离源(APCI 源),定量分析离子分别为m／z 427．9(莫雷西嗪)和m／z 326．9(氯氮平)。结果 线性范围为10．0-4 000 ng·mL-1,萃取回收率在(72．74±3．61)％,日内、 日间的RSD皆<15％;用3P97计算主要药代动力学,经双因素方差分析:tmax为 (1．46±0．38)h;Cmax为(550．8±279．3)ng·mL-1;t1／2为(2．41±0．92)h;用 梯形法计算,AUC0-t和AUC0-∞分别为(1 529．4±726．7),(1 585．3±740．7)ng ·h·mL-1。结论 本方法适于测定血浆中莫雷西嗪浓度及其进行人体生物 等效性研究。