电位滴定法标定高氯酸滴定液及其应用

目的:建立一种用电位滴定法标定高氯酸滴定液的分析方法,并将其结果运用于多种化学原料药的分析。方法:采用电位滴定对高氯酸滴定液(用DG113-SC电极)进行标定,再以相同方法测定盐酸多巴酚丁胺、硝酸硫胺和甘氨酸的含量。结果:用电位滴定法标定,线性关系好(r=0.9999),精确度更高,重复性更好,并且可以避免人为视觉误差。用电位滴定法标定与传统的酸碱指示剂法标定相比,两者之间存在一定差异。将其运用到化学原料药的分析,两种标定方法的结果对含量测定存在系统误差。结论:在药物分析过程中,对于使用电位滴定法测定药品含量的滴定液,应使用电位滴定法来标定其浓度,可以减小方法误差,使测量结果更严密。     

醋酸地塞米松凝胶剂的制备及含量测定

目的:制备0.1％醋酸地塞米松外用凝胶剂,并建立该制剂的含量测定方法。方法:以1％卡波普为凝胶基质,制备醋酸地塞米松外用凝胶剂。采用氯仿萃取、显色后比色法测定醋酸地塞米松含量。结果:本制剂易制备,含量测定方法可靠,平均回收率为100.4％(RSD=1.18％)。结论:该制剂适合临床使用,含量测定方法简单可行,适合凝胶剂中含羰基甾休类药物的提取分离及含量测定。     

紫外分光光度法测定盐酸普鲁卡因注射液的含量

目的建立紫外分光度法测定盐酸普鲁卡因注射液含量测定方法.方法采用紫外分光度法测定盐酸普鲁卡因注射液的含量,测定波长为(290±1)nm.结果线性范围为4～12 mg·L-1,盐酸普鲁卡因的平均回收率为99.7%,RSD=0.34%(n=3),r=0.9999(n=5).结论该法简便、快速、准确,可作为盐酸普鲁卡因注射液的含量测定方法.     

痱子粉中氧化锌含量测定方法的改进

目的 对痱子粉中氧化锌含量测定方法进行改进。方法 采用二甲酚橙为指示剂,醋酸-醋酸铵(p H=6.0)为缓冲液,乙二胺四醋酸二钠(0.05 mol·L^-1)为配位剂的方法直接测定。结果 用改进后的含量测定方法简化了一系列操作步骤,滴定终点突跃明显,且滑石粉对试验结果不产生干扰,标准曲线回归方程为y=239.0x+0.278,r=1.0000,表明氧化锌的取样量在0.06～0.14 g范围内,与乙二胺四醋酸二钠滴定液(0.05 mol·L^-1)的消耗体积具有良好的线性关系,平均重复性RSD为0.35%,平均加样回收率为99.76%(RSD=0.26%)。结论 该试验所采用的含量测定方法较原方法简单,结果更准确、可靠,可用于痱子粉中氧化锌含量的测定。     

HPLC法测定注射用阿奇霉素枸橼酸二氢钠的含量及有关物质

目的:建立注射用阿奇霉素枸橼酸二氢钠含量和有关物质的测定方法。方法:采用高效液相色谱法,并与该制剂标准采用的含量测定方法(抗生素微生物检定法)及有关物质检查方法(薄层色谱法)测定结果进行比较。色谱柱为资生堂C18MGⅡ柱,流动相为磷酸盐缓冲液(pH8.2)-乙腈(45:55,V/V),流速为1.0ml/min,检测波长为215nm,柱温为35℃。结果:阿奇霉素检测质量浓度线性范围为0.5～3.0mg/m(lr=0.9999),平均回收率为100.2%,RSD=0.7%(n=9)。本方法主药含量测定结果与原标准方法结果一致,有关物质检查方法优于原标准方法。结论:建立的方法简便、准确、专属性强、重复性好,可用于注射用阿奇霉素枸橼酸二氢钠含量及有关物质的测定。     

紫外分光光度法测定芦丁控释片含量

目的成立芦丁控释片的含量测定方法。方法使用紫外分光光度法,测定波长255nm。结果线性范围3～18μg/mL,均回收率为99.31%,RSD=0.28%(n=6)。结论该方法简便、灵敏,可以用于芦丁控释片质量控制。     

高效液相色谱法测定右旋糖酐40葡萄糖注射液的含量

目的:探讨测定右旋糖酐40葡萄糖注射液的含量测定方法.方法:利用2000年版<中国药典>右旋糖酐分子量与分子量分布检查法,在测定分子量与分子量分布的同时,测定右旋糖酐40葡萄糖注射液中右旋糖酐、葡萄糖的含量.结果:右旋糖酐、葡萄糖的平均回收率分别为101.2%(RSD=1.0%,n=3)和100.5%(RSD=0.8%,n=3).结论:该方法可作为右旋糖酐40葡萄糖注射液含量测定的内控检测方法.     

果糖二磷酸钠片含量测定方法研究

目的 建立果糖二磷酸钠片含量测定方法.方法 采用酶法测定含量,通过使用还原型烟酰胺腺嘌呤二核苷酸(NADH)、3-磷酸甘油脱氢酶-磷酸丙糖异构酶(GDH-TIM)﹑醛缩酶(ALD)催化果糖二磷酸钠降解,在340 nm波长处测定其吸收度.结果 果糖二磷酸钠在0～400 mg· L-1范围内呈良好的线性关系(r=0.999 5 ),平均回收率为99.04%(RSD=0.57%,n=9).结论 该方法灵敏﹑准确,重复性好,能满足果糖二磷酸钠片含量测定的要求.     

延龄草鞣质的含量测定

目的:建立延龄草中鞣质的含量测定方法。方法:以磷钼钨酸法作为显色方法,采用紫外-可见分光光度法进行测定。结果:在0.0755~0.2012mg范围内吸光度与鞣质含量呈良好的线性关系(r2=0.9991,n=9),平均回收率为100.10%,RSD=2.51%,n=9。结论:该法精密度、重现性良好,可作为延龄草中鞣质的含量测定方法。     

紫外分光光度法测定抗乳腺增生乳膏中达那唑的含量

目的建立抗乳腺增生乳膏中达那唑的含量测定方法。方法采用紫外分光光度法,测定波长为285nm。结果达那唑检测浓度在5～25μg/ml范围内线性关系良好(r=0.9999),平均回收率为99.2%(RSD=0.32%,n=5)。结论本方法简便、快速、准确,可用于该制剂的含量测定与质量控制。     

非洛地平与螺内酯合用对大鼠肾性高血压的治疗作用

目的观察非洛地平（Ｆｅｌｏ）和螺内酯（Ｓｐｉｒ）合用对高血压大鼠的动脉收缩压（ＳＢＰ）、左室肥厚及左室心肌纤维化和血浆肾素、血管紧张素、醛固酮水平的作用。方法采用两肾一夹Ｇｏｌｄｂｌｏｔｔ高血压模型，尾容积法测定清醒大鼠动脉收缩压；分离左心室并称重，测定其羟脯氨酸，计算胶原蛋白含量。结果与模型对照组比较，Ｆｅｌｏ＋Ｓｐｉｒ组ＳＢＰ、左心室重与体重的比（ＬＶＷ／Ｗ）及左心室胶原蛋白含量分别下降了４４．５％，３２．８％，３２．０％；Ｆｅｌｏ组分别下降了３６．６％，１９．６％，１０．３％。结论本实验结果提示，Ｆｅｌｏ和Ｓｐｉｒ在降低肾性高血压大鼠的ＳＢＰ、抑制其左心室肥厚、心肌纤维化方面有协同作用。     

气相色谱法测定人血浆中非洛地平浓度及药代动力学

采用气相色谱—电子捕获检测法测定人血浆中非洛地平浓度,研究中国男性正常人口服该药的药代动力学规律,为临床用药提供依据。血浆样品经乙醚—正己烷(2∶1)萃取浓缩后进行测定。结果表明非洛地平浓度在0.5～10ng·ml^-1范围内线性良好(γ=0.9991)。此法简便易行,精密度好,日内、日间的RSD分别小于5.09%及8.62%。回收率平均为97.3%±4.0%。测定了10名健康者单次口服非洛地平10mg后不同时间的血药浓度并计算了相应的药代动力学参数。     

A comparison of felodipine and propranolol as additions to hydrochlorothiazide in the treatment of hypertension

Summary Eighty one patients with uncomplicated hypertension who required additional antihypertensive medication (diastolic Phase V [dBP]95 mm Hg) after 4 weeks treatment with hydrochlorothiazide (HCTZ) 25 mg o.m. were randomized to receive felodipine 5 mg b.i.d. (n=40) or propranolol (n=41) 80 mg b.i.d. in addition to HCTZ 25 mg o.m. If the dBP measured about 12 h post-dose was not 90 mm Hg after 4 weeks, the dose of felodipine or propranolol was doubled. The double blind trial period was 8 weeks for all patients.Over the 8 week period, felodipine reduced the seated dBP from 100 to 83 mm Hg and propranolol from 101 to 86 mm Hg. The attained seated dBPs were significantly different in the two groups. About one third of patients in each group received the high dose of second-line therapy. After 8 weeks 91% of patients receiving HCTZ+felodipine and 84% receiving HCTZ+propranolol had a dBP 90 mm Hg. Both regimens were well-tolerated with an equal incidence but different pattern of adverse events (felodipine: flushing, headache and peripheral oedema; propranolol: dyspepsia, fatigue and vasospasm).In this 8-week study, felodipine and propranolol were safe and effective second-line antihypertensive drugs when added to hydrochlorothiazide. At the doses selected, felodipine was at least as effective as propranolol.     

Vascular-selective effect of lercanidipine and other 1,4-dihydropyridines in isolated rabbit tissues.

The aim of this study was to characterize the in-vitro vasoselectivity of lercanidipine (in comparison with lacidipine, amlodipine, nitrendipine and felodipine) by evaluating its functional calcium antagonistic activity on rabbit vascular (aorta) and cardiac tissues (heart ventricle). Although incubation with all the compounds tested elicited a concentration-dependent relaxant effect on vascular tissue precontracted with KCl (80 mM), 50% relaxation was reached at different times for each concentration and drug tested. At 10 nM concentration 50% relaxation was reached after 210 min with lercanidipine, 278 min with amlodipine, 135 min with lacidipine, 75 min with nitrendipine and 70 min with felodipine. The onset of the effect was, therefore, similar for lercanidipine, amlodipine and lacidipine, but faster for nitrendipine and felodipine. Similarly, all the compounds tested concentration-dependently reduced the force of cardiac contraction (negative inotropic activity). In this model, the time needed to reach 50% reduction in contractile force was also concentration-dependent, and the ranking order of the speed of onset of the effect (evaluated as the ratio of the IC50 values (the concentrations inhibiting contraction by 50%) calculated after 1 and 4 h incubation) was lacidipine (3.8) > amlodipine (9.6) > felodipine (39) > lercanidipine (68) = nitrendipine (89). The vasoselectivity, expressed as the ratio of the IC50 values obtained on cardiac and vascular tissue, were (for 4 h incubation) 730, 193, 95, 6 and 3 for lercanidipine, lacidipine, amlodipine, felodipine and nitrendipine, respectively, showing that lercanidipine is the most vasoselective of the calcium-antagonists tested. The results show that lercanidipine reduces the inotropic force of the rabbit heart to a lesser extent than do other calcium antagonists, and that this drug had the best heart/vessel selectivity index among the compounds tested at all the times tested.     

Effects of felodipine on microvascular resting tone and responses to nerve stimulation and perfusion pressure reduction in rabbit skeletal muscle.

The effects of felodipine, a vasoselective dihydropyridine calcium antagonist, on microvascular dynamics were investigated in skeletal muscle. The diameters of the transverse (10-28 microns) and terminal (4-8 microns) arterioles, located at the immediate precapillary level in the rabbit tenuissimus muscle, were registrated by intravital microscopy. Topical application of felodipine (10(-7)-10(-5) M) induced a concentration-dependent vasodilation of both arteriolar generations. The steady state response at 10(-7) M revealed a relatively more pronounced dilatation of transverse (92 +/- 30% increase in diameter) than of terminal arterioles (44 +/- 12%). This is in contrast to muscle exercise, which elicits a more pronounced dilatation of terminal (260 +/- 39% increase) than of transverse arterioles (103 +/- 15%). Vasomotor nerve stimulation evoked a frequency-dependent constriction both in the absence and presence of felodipine (10(-6) M). However, the vasodilatory response elicited by graded perfusion pressure reductions was eliminated in the presence of felodipine (10(-7) M). Thus, the vasomotor nerve response was better preserved than the autoregulatory response in the presence of the calcium antagonist. The results indicate that felodipine dilates arterioles via an inhibition of myogenic vascular reactivity, which supports previous results obtained both in vivo and in vitro.     

缬沙坦单用及合用治疗老年高血压病的疗效观察

目的:观察缬沙坦单用及与福辛普利或非洛地平合用对老年高血压的降压疗效。方法:80例老年轻、中度高血压患者,经过2周安慰剂清洗期后,单服缬沙坦80 mg,qd。4周后随机分2组,分别联合服用福辛普利10 mg,qd,或非洛地平5 mg, qd,均为4周。治疗前及治疗后4周和8周行24 h动态血压监测,并测治疗前后坐位血压。结果:缬沙坦单用4周后,坐位血压和24 h动态血压均下降(P<0．01或P<0．05)。缬沙坦与福辛普利或非洛地平合用4 wk后坐位血压总有效率从45％增加为88％和85％;动态血压显示联合用药降压作用较明显。结论:缬沙坦单用有长效的降压作用,与福辛普利或非洛地平联合用药有叠加降压作用。     

微波消解-ICP-OES法测定水獭肝中的铁、锌、铜和镁含量

目的建立水獭肝中Fe、Zn、Cu和Mg 4种无机元素含量的分析方法。方法采用微波消解电感耦合等离子体原子发射光谱法(ICP-OES)法测定水獭肝中4种重金属元素,用国家生物成分分析标准物质黄芪验证方法的准确度。结果该方法线性良好,相关系数均≥0.999 9,相对标准偏差(n=6)≤2.0%,回收率在97%~103%之间,标准物质黄芪的测定值与标准值基本吻合。结论该方法快速、准确、灵敏度高,可以用于水獭肝中的铁、锌、铜、镁的测定。     

LC-MS/MS法测定人血浆中非洛地平的浓度

目的:建立人血浆中非洛地平浓度的LC-MS/MS测定方法,并将其应用于临床试验中非洛地平血药浓度的测定。方法:以尼莫地平为内标,人血浆样品经乙醚-正己烷(1∶1,v/v)萃取处理后,进行LC-MS/MS分析。采用Hypersil BOS-C18(150 mm×2.1 mm,5μm)色谱柱,流动相为乙腈-0.1%甲酸水溶液(12∶88,v/v);使用电喷雾离子源(ESI),正离子多反应监测(MRM)模式检测,用于定量分析的非洛地平和内标尼莫地平的监测离子分别为m/z 384.1→338.0和m/z 419.0→301.1。结果:4.5 min完成1次分析,血浆内源性物质对测定无干扰,非洛地平在0.1038～10.38μg.L-1浓度范围内线性关系良好(r2>0.99),定量下限为0.1038μg.L-1,批内精密度(RSD)不大于9.6%,批间精密度(RSD)不大于10.4%。非洛地平与内标化合物的平均提取回收率分别为99.4%和103.5%,平均基质效应分别为110.1%和108.4%,且均不存在显著浓度依赖性。结论:本文所建立的方法准确快速,灵敏度高,专属性强,可用于临床试验中非洛地平制剂低剂量给药后非洛地平血药浓度的测定。     

Enantioselective determination of felodipine in human plasma by chiral normal-phase liquid chromatography and electrospray ionisation mass spectrometry.

An analytical method was developed for the determination of the enantiomers of felodipine, a dihydropyridine-type calcium antagonist, in human blood plasma. Felodipine was extracted from plasma using toluene as extraction solvent. The enantiomers were separated on a cellulose tris(4-methyl benzoate) stationary phase (Chiralcel OJ-R) using 2-propanol-iso-hexane (11:89) as mobile phase. Post-column addition of ammonium acetate in ethanol-water (95:5) allowed sensitive detection of the ammonium adduct by electrospray ionisation and selected reaction monitoring. Deuterated felodipine racemate was used as internal standard. Within-run repeatability was determined and a coefficient of variation below 2% was achieved at 22 nmol/l and below 10% at 0.27 nmol/l. Between-day precision was evaluated and a coefficient of variation of 3.6% at 4 nmol/l plasma was obtained. Limit of quantification (LOQ) was set at 0.25 nmol/l (0.10 microg/l). The method proved adequate for pharmacokinetic studies of R- and S-felodipine after oral administration of therapeutic doses of felodipine.     

Plasma concentration-effect relationship of felodipine intravenously in patients with congestive heart failure

The pharmacodynamics of felodipine were analyzed in patients with congestive heart failure in a randomized, double-blind, placebo-controlled study. Felodipine at a dose of 1 mg (n = 11) or placebo (n = 12) was given intravenously during a 60-min period. Hemodynamic measurements and plasma samples were obtained every 15 min during a 2-hour period. An increase in heart rate (HR, +8%, p less than 0.01) and cardiac output (CO, +36%, p less than 0.001), and a decrease in mean arterial pressure (MAP, -24%, p less than 0.001) and systemic vascular resistance (SVR, -46%, p less than 0.001), were found. Pulmonary artery, right atrial, wedge pressure, and stroke-work index did not change. Linear regression analysis showed a significant correlation between felodipine plasma levels and changes in HR (r = 0.71, p less than 0.05), MAP (r = 0.94, p less than 0.01), CO (r = 0.73, p less than 0.05), and SVR (r = 0.88, p less than 0.01). A strong hyperbolic correlation was demonstrated between individual plasma levels and changes in MAP (r = 0.97, p less than 0.001). Hysteresis analysis showed that plasma levels are directly related to the concentration at the receptor site. A clockwise hysteresis was found in HR, CO, and SVR, but not in MAP. It is concluded that changes in flow and resistance are based on a physiological adjustment, a baroreflex-mediated response to vasodilation induced by felodipine, resulting in MAPs that remain closely related to felodipine plasma levels over a wide range.