盐酸维拉帕米注射液的含量及有关物质的HPLC测定

目的:建立测定盐酸维拉帕米注射液含量及有关物质的HPLC法.方法:采用Phenomenex ODS-3 C18柱,(150mm×4.6mm, 5μm),甲醇:醋酸-醋酸钠-三乙胺溶液(取醋酸钠1.36g,加水适量,摇振使溶解,加冰醋酸33mL,三乙胺20mL,加水稀释至1 000mL,摇匀)(58∶42)为流动相,检测波长为278nm;流速:1.0mL*min-1.结果:盐酸维拉帕米在浓度67.4～115.56μg*mL-1范围内线性关系良好,相关系数r=0.999 9.平均回收率:99.90%,RSD=0.22%.结论:本方法快速,准确,可作为盐酸维拉帕米注射液的质控标准.     

HPLC法测定盐酸维拉帕米片的溶出度

目的建立盐酸维拉帕米片溶出度的高效液相色谱(HPLC)测定方法。方法色谱柱为phenomenex C18(5μm,250mm×4.6mm);流动相为醋酸—醋酸钠溶液—甲醇—三乙胺(55∶45∶1);流速为1.0ml/min;检测波长为278nm;柱温为40℃。结果在10.67～85.36μg/ml的范围内,其浓度与峰面积呈良好的线性关系(r=1);盐酸维拉帕米在24h内稳定性良好,HPLC重现性良好;平均回收率为100%,相对标准偏差为0.5%。结论 HPLC方法准确、可靠、专属性强,可用于盐酸维拉帕米片的溶出度测定。     

高效液相色谱法测定注射用盐酸维拉帕米的含量

目的建立测定注射用盐酸维拉帕米含量的高效液相色谱法。方法采用C18色谱柱（150mm×4．6mm，5μm），以醋酸-醋酸钠溶液-甲醇-三乙胺（55：45：1）为流动相，检测波长为278nm。结果盐酸维拉帕米进样量在1．0～10.0μg范围内与峰面积线性关系良好，r=0．9998，平均回收率为99．75％，RSD为0．93％。结论高效液相色谱法精密可靠，可作为注射用盐酸维拉帕米的质量控制方法。     

HPLC测定人肝转基因细胞中的盐酸维拉帕米

目的为了研究盐酸维拉帕米经人肝CYP450转基因细胞的代谢,建立了反相高效液相色谱的测定方法.方法与人肝转基因细胞提取的S9上清液孵育之后的样品用二氯甲烷-异丙醇(9∶1,V/V)提取,采用地西泮作为内标,以Shim-packCLC-ODSC18为色谱柱,甲醇-水-三乙胺(60∶40∶0.4,V/V),pH6.4为流动相,紫外检测波长为235nm,流速0.5ml*min-1.结果维拉帕米浓度在5～320μg*ml-1范围内线性关系良好,r=0.9999,n=6.检测限为6.25ng(S/N≥3),定量限为9.4ng±1.06ng,相对标准偏差(RSD)＜12%(n=5).方法回收率达94.4～99.6%,日内、日间RSD分别为5.9～2.9%,5.2～3.8%(n=5).结论此方法简便、准确,可用于研究盐酸维拉帕米在人肝转基因细胞中的代谢.     

盐酸维拉帕米缓释微球含量的测定及体外释放行为研究

目的建立UV法测定盐酸维拉帕米缓释微球含量的方法,考察环境pH对微球释药行为的影响。方法采用UV法测定缓释微球中盐酸维拉帕米,对该方法的专属性、精密度、回收率、稳定性等进行考察;并测定维拉帕米微球在蒸馏水、0.1 mol·L^-1盐酸、pH=6.8磷酸盐缓冲液3种不同的释放介质中的累积释放度,采用f2相似因子法对不同释放介质药物释放曲线的相似性进行评价。结果不同介质中的盐酸维拉帕米在229 nm处,吸光度A值和浓度C间线性关系均良好,线性范围为7.5～22.5μg mL-1,r值为0.999 9,平均回收率的RSD值均〈2%。结论该方法操作简便快捷,结果准确可靠,可用于盐酸维拉帕米缓释微球的含量测定,缓释微球在蒸馏水、pH=6.8磷酸盐缓冲液中的累积释放度基本一致,在0.1 mol·L^-1盐酸中释放较快。     

HPLC测定脂溶性前列安栓中盐酸小檗碱的含量

目的 建立一种简便的测定脂溶性前列安栓中盐酸小檗碱含量的方法.方法 采用高效液相色谱法(HPLC)测定盐酸小檗碱的含量.色谱条件为Kromasil C18 柱( 4.6 mm × 200 mm,5 μm), 流动相为乙腈-0.1%磷酸溶液(50:50)(每100 ml中加入十二烷基硫酸钠0.1 g ),检测波长350 nm.供试品预处理采用超声溶解法.结果 盐酸小檗碱在20～200 μg·ml-1范围内有良好的线性关系(r=0.9999),平均回收率为98.9%,RSD为0.5%.结论 本方法可用于脂溶性前列安栓中盐酸小檗碱的含量测定,方法简便、快速、灵敏.     

高效液相色谱法测定稳心颗粒中非法添加药物的含量

目的建立检测稳心颗粒中非法添加的盐酸普萘洛尔、盐酸维拉帕米和盐酸普罗帕酮含量的高效液相色谱法。方法采用Inertsil ODS—SP C18色谱柱（250mm×4．6mm,5μm）,流动相为磷酸盐缓冲液（取磷酸二氢钾6．8g,辛烷磺酸钠1．3g,加水溶解并稀释至1000mL,用磷酸调节pH至3．0）-甲醇（40：60）,流速为O．8mL／min,检测波长为223nm,柱温为25℃。结果盐酸普萘洛尔、盐酸维拉帕米和盐酸普罗帕酮进样量的线性范围分别为0．01976～2．47μg（r=1）,0．01～2．5μg（r=1）和0．009948～2．487μg（r=1）;平均回收率分别为97．11％,97．63％和98．88％,RSD分别为1．85％,1．92％和1．46％（n=6）。结论该方法准确、重现性好,可作为稳心颗粒中非法添加盐酸普茶洛尔、盐酸维拉帕米和盐酸普罗帕酮的有效检测方法。     

盐酸维拉帕米的流动注射化学发光法测定

目的:建立快速测定盐酸维拉帕米的方法。方法:在碱性介质中,M-氯代丁二酰亚胺(NCS)能与鲁米诺产生化学发光。本文发现盐酸维拉帕米对 NCS-鲁米诺化学发光反应体系有很强的增敏作用,由此建立了盐酸维拉帕米流动注射化学发光测定的新方法。结果:所建方法的线性范围为2.0×10~(-8)～1.0×10~(-6)g·mL~(-1)(r=0.9981),检出限为5×10~(-9)·mL~(-1),相对标准偏差为2.3%(C=4.0×10~(-7)g·mL~(-1),n=11)。结论:此法已用于药品盐酸维拉帕米的测定,用药典方法进行对照,结果无显著性的差异。     

高效液相色谱法同时测定盐酸维拉帕米及其主要代谢产物

建立了反相高效液相色谱法同时测定人血浆中维拉帕米及其主要代谢产物去甲维拉帕米血药浓度.以甲醇—水—三乙胺(67∶33∶0.4,pH6.7)为流动相,乙吗噻嗪(ethmosine)为内标,样品用正己烷—正丁醇混合液提取浓缩后进样,紫外检测器检测(279nm)。此法操作简便,精密度好,日内、日间误差:维拉帕米<8.6%,去甲维拉帕米<7.6%;方法回收率高,维拉帕米、去甲维拉帕米回收率均>92%。两者血药浓度在25～1000ng·ml-1范围内呈线性关系,最小检测浓度维拉帕米:2.5ng·ml^-1,去甲维拉帕米:5.0ng·ml^-1。应用该法测定了6名志愿者口服盐酸维拉帕米片剂后的血药浓度。     

HPLC测定脂溶性前列安栓中盐酸小檗碱的含量

目的建立一种简便的测定脂溶性前列安栓中盐酸小檗碱含量的方法。方法采用高效液相色谱法(HPLC)测定盐酸小檗碱的含量。色谱条件为Krom asil C18柱(4.6 mm×200 mm,5μm),流动相为乙腈-0.1%磷酸溶液(50∶50)(每100m l中加入十二烷基硫酸钠0.1 g),检测波长350 nm。供试品预处理采用超声溶解法。结果盐酸小檗碱在20~200μg.m l-1范围内有良好的线性关系(r=0.9999),平均回收率为98.9%,RSD为0.5%。结论本方法可用于脂溶性前列安栓中盐酸小檗碱的含量测定,方法简便、快速、灵敏。     

Verapamil and breast-feeding

Summary Concentrations of verapamil and norverapamil were measured in the plasma and breast milk of a woman receiving 120 mg verapamil three times daily. Whilst the concentrations of verapamil in breast milk averaged about 64% of those in maternal plasma no drug could be detected in the plasma of the infant. It is concluded that maternal therapy with verapamil does not pose a hazard to the suckling infant.     

Verapamil acute self-poisoning.

A previously healthy girl, without heart disease, who ingested 2400 mg of verapamil developed hypotension, trifasicular block pattern, mental confusion, mild metabolic acidosis, and hyperglycemia. She recovered with symptomatic and supportive therapy. A discussion is presented about the action mechanism of the drug.     

维拉帕米对丛集性头痛发作的预防作用

目的 研究维拉帕米对丛集性头痛(Cluster Headache,CH)发作及头痛程度的影响,为CH的防治提供参考.方法 将60例CH患者随机分为对照组与实验组,每组30例.对照组给予强的松、氟桂利嗪、高压氧等常规治疗,实验组在常规治疗基础上加用维拉帕米,3次/d,持续用药3周.记录用药1周、2周、3周后CH发作频率,采用视觉模拟评分法(VAS)评价头痛程度,采用心境状态量表(POMS)及WHO简易生活质量量表-BREF(WHOQOL-BREF)评价患者情绪及生活质量变化,治疗前、后测量患者血浆5-羟色胺(5-HT)、降钙素基因相关肽(CGRP)水平变化.结果 治疗2周、3周后,实验组头痛发作次数少于对照组(P＜0.05);治疗1周、2周、3周后,实验组头痛VAS评分均低于对照组(P＜0.05);两组治疗后除了愤怒评分比较差异无统计学意义(P＞0.05)外,实验组焦虑、抑郁、疲劳、精力评分均低于对照组(P＜0.05);实验组治疗后生理功能、心理功能、社会功能及总体健康评分均高于对照组(P＜0.05);实验组治疗后5-HT浓度高于对照组,而CGRP低于对照组(P＜0.05).结论 维拉帕米治疗CH可减少头痛发作次数,减轻头痛程度,改善患者生活质量,对CH发作有一定的预防作用.     

Verapamil analogues with restricted molecular flexibility

Three analogues with restricted flexibility were designed to study the active conformation of verapamil during interaction with the slow calcium channel. Thus cis- and trans-1-(3,4-dimethoxyphenyl)-4-[N-[2-(3,4-dimethoxy-phenyl)ethyl]-N- methylamino]-r-1-cyclohexanecarbonitrile (5a and 5b), and 4-(3,4-dimethoxyphenyl)-N-[2-(3,4-dimethoxyphenyl)ethyl]-4-cyanopiper idine, in which the verapamil structure is inserted into a cyclohexane or piperidine ring, were synthesized. Conformational analysis was performed with NMR and theoretical methods, and slow calcium channel antagonism was tested on guinea pig aorta strips. The compounds are some 100 times less potent than the parent compound even if they are able to reach conformations that are quite close to the lowest energy conformation proposed for verapamil and similar compounds. It appears that the flexibility to rotate around the bond between the quaternary atom and the adjacent methylene, a property which is lost in compounds 5a, 5b, and 6, is a major requisite for the calcium antagonism of verapamil.     

Verapamil in the treatment of hypertension

A randomized, double-blind, crossover trial was carried out in 17 hypertensive patients to evaluate the hypotensive efficacy and safety of verapamil. Verapamil in doses of 120 mg thrice daily was compared with pindolol in doses of 7.5 mg twice daily. A thiazide diuretic was given with both drugs. Blood pressure fell about 14/11 mm Hg during treatment with either drug compared to the placebo period, and neither drug caused significant side effects. Verapamil did not affect plasma renin concentration.     

Verapamil block of T-type calcium channels

Verapamil is a prototypical phenylalkylamine (PAA), and it was the first calcium channel blocker to be used clinically. It tonically blocks L-type channels in the inner pore with micromolar affinity, and its affinity increases at depolarized membrane potentials. In T-type calcium channels, verapamil blocks with micromolar affinity and has modestly increased affinity at depolarized potentials. We found that a related PAA, 4-desmethoxyverapamil (D888), is comparable with verapamil both in affinity and in state-dependence. Permanently charged verapamil was more effective intracellularly than neutral verapamil. Charged PAAs were able to access their binding site from both inside and outside the cell. Furthermore, membrane-impermeant [2-(trimethylammonium)ethyl]methanethiosulfonate was able to access the inner pore from outside of the cell. We examined a homology model of the T-type calcium channel to look for possible routes of drug entry. Mutation of L1825W produced a channel that was blocked significantly more slowly by charged verapamil from the outside, with an increase in apparent affinity when the drug was applied from the inside. Data suggest that T-type channels have a back pathway through which charged drugs can access the inner pore of the channel without passing through the plasma membrane.