高效液相梯度洗脱法测定注射用别嘌醇钠中的有关物质

目的建立测定注射用别嘌醇钠有关物质的高效液相梯度洗脱法。方法采用ODS C18色谱柱(250 mm×6 mm,5μm),以1.25 g.L-1磷酸二氢钾-甲醇(体积比为90∶10~70∶30)为流动相进行梯度洗脱,柱温为30℃,流速为1.0 mL.min-1,检测波长为230 nm。结果在上述色谱条件下,5种杂质(1-5)能与别嘌醇得到有效分离,分离度大于1.5;检测限为4.5 ng,精密度良好(RSD为0.71%)。结论高效液相梯度洗脱法可用于测定注射用别嘌醇钠中的有关物质。     

高效液相色谱法测定注射用头孢地嗪钠有关物质Ⅱ(聚合物)及其方法学研究

目的 采用高效液相色谱法测定注射用头孢地嗪钠有关物质Ⅱ(聚合物),并进行了方法学研究.方法 以适合分离分子量为1 000～5 000球状蛋白的色谱用亲水硅胶为填充剂,磷酸盐缓冲液(pH=7.0)[0.005 mol·L-1磷酸氢二钠溶液-0.005 mol·L-1磷酸二氢钠溶液(61:39)]-乙腈(95:5)为流动相...     

高效液相色谱法测定头孢地尼有关物质

目的:建立高效液相色谱法测定头孢地尼的有关物质.方法:采用迪马ODS (150 mm×4.6 mm,5 μm)色谱柱;流动相:A [0.25%四甲基氢氧化铵溶液(用10%磷酸溶液调节pH值至5.5)1 000 ml,加入0.1 mol/L乙二胺四醋酸二钠0.4 ml],B[ 0.25%四甲基氢氧化铵溶液(用10%磷酸溶液调节pH值至5.5)-乙腈-甲醇(500:300:200), 加入0.1 mol/L乙二胺四醋酸二钠0.4 ml]进行梯度洗脱;流速为0.9 ml/min;检测波长为254 nm;柱温为40 ℃.结果:头孢地尼线性范围为7.64～76.40 μg/ml(r=0.999 9).结论:该方法准确可靠,可控制头孢地尼的有关物质.     

HPLC法测定醋氯芬酸中有关物质

目的 建立高效液相色谱法测定醋氯芬酸中的有关物质.方法 采用C18色谱柱,流动相A:磷酸钠盐缓冲液(称取1.12 g磷酸,加入1000 mL水中,以1 mol·L-1氢氧化钠溶液调节pH至7.0)和流动相B:乙腈-水(90:10),梯度洗脱,检测波长:275 nm.结果 醋氯芬酸与有关物质达基线分离.结论 本方法本法简便、灵敏、准确.     

反相高效液相色谱梯度洗脱法测定厄他培南钠的含量和有关物质

目的 建立反相高效液相色谱梯度洗脱法测定厄他培南钠含量及有关物质的方法.方法 采用Inertsil ODS C18柱(250mm×4.6mm,5μm),0.01 mol/L乙酸铵溶液为流动相A,乙腈为流动相B,梯度洗脱,流速为1.0mL/min,柱温25℃,检测波长为230nm.结果 厄他培南在0.17～0.87mg/mL范围内线性关系良好,r=0.9997,最低检测浓度为17ng/mL,噁嗪酮、Promaba、开环降解物和二聚物等有关物质在该色谱条件下均分离良好.结论 本法重现性好,专属性强,可用于测定厄他培南钠的含量和有关物质.     

反相高效液相色谱法测定头孢美唑钠中的有关物质

目的:建立反相高效液相色谱法测定头孢美唑钠中的有关物质。方法:采用Diamonsil-C18色谱柱(250 mm×4.6 mm,5μm),以0.08 mol.L-1醋酸铵溶液-甲醇(85∶15)(混合后,冰醋酸调pH至6.0)为流动相,流速为1 mL.min-1,检测波长为214 nm,柱温为30℃;以主要杂质TMT为对照,量化样品中的相应杂质,以头孢美唑钠为对照,量化其他杂质。结果:头孢美唑钠与各有关物质分离良好;TMT和头孢美唑钠分别在0.01024~102.40μg.mL-1和0.02μg.mL-1~1.00 mg.mL-1浓度范围内,峰面积与浓度呈良好的线性关系,相关系数均为0.999 9,TMT和头孢美唑钠的检测限分别为0.05 ng和0.2 ng,TMT的平均回收率为100.21%,中间精密度为3.66%(n=6)。结论:本法简便、专属,灵敏,可用于头孢美唑钠有关物质的测定。     

HPLC法测定注射用头孢尼西钠的含量

目的建立用HPLC法测定注射用头孢尼西钠含量的测定方法.方法采用高效液相色谱法,以0.01 mol·L-1磷酸盐溶液-乙腈(75:25)为流动相,检测波长261 nm,流速1ml·min-1.结果头孢尼西钠线性浓度范围在60～140mg·L-4.r=0.999 9.结论该方法简便、灵敏、准确,专属性强.     

培美曲塞二钠中有关物质HPLC检测方法的改进

目的建立测定培美曲塞二钠中有关物质的高效液相色谱法。方法采用HPLC梯度洗脱法,采用Shim-Pack VP-ODS色谱柱(150 mm×4.6 mm,5μm)色谱柱,以0.02 mol.L-1磷酸铵溶液(用磷酸调pH值至4.0)为流动相A,乙腈为流动相B;流速为1.0 mL.min-1;检测波长为240 nm;进样体积:20μL。结果样品中有关物质应小于1.0%,单个杂质应小于0.5%。结论改进后的方法可较好的分离培美曲塞二钠的各主要杂质,真实反映药品质量,有助于发现产品中的质量问题,进而促使产品质量的提高。     

HPLC法测定西他沙星的含量及有关物质

目的建立测定西他沙星含量及有关物质的HPLC法。方法采用C18色谱柱,以0.05 mol·L-1磷酸二氢钾和0.05mol·L-1乙酸铵(磷酸调pH2.2)-乙腈=3∶1为流动相,西他沙星含量采用等度洗脱,有关物质采用梯度洗脱,流速1.0 ml·min-1,检测波长286 nm,柱温30℃。结果西他沙星在22.64～113.20 mg·L-1范围内呈良好线性关系(r=0.9999)。有关物质检测限为0.55 ng,各杂质峰与主峰分离良好。结论该法简单方便,准确灵敏,可用于测定西他沙星含量及有关物质。     

注射用盐酸头孢替安有关物质测定方法的改进

目的：改进注射用盐酸头孢替安的有关物质测定方法。方法：采用高效液相色谱法。色谱柱为Phenomenex C18色谱柱,流动相A为0.05 mol·L-1磷酸盐缓冲液（pH值7.6～7.8）,流动相B为乙腈,梯度洗脱,流速为1.0 mL·min-1,柱温为25 ℃,检测波长为254 nm,进样量为20 μL。结果：在该条件下头孢替安峰与各有关物质峰分离良好。检测限为63 ng·mL-1。结论：优化后的方法采用梯度洗脱法,较等度洗脱法提高了杂质分离度和检出率;对供试品溶样液进行了比较,简化了试验操作步骤;优化了系统适用性试验条件,为其产品质量提高提供了依据。     

对临床试验中显著性检验、区间检验及置信区间检验之间关系一致性的认识

显著性检验是最基本的统计假设检验,它的基本思想是小概率原理;区间检验是传统显著性检验的延伸,它用来检验两个总体的差异是否在某范围之内;置信区间检验是先找到药物疗效差值的置信区间,通过置信区间下限或(和)上限与界值的关系来判断两种药物非劣效、等效、优效的关系。通过公式推导发现,区间检验与显著性检验的主要区别是前者的假设中包含了有临床意义的界值△,而区间检验和置信区间检验是一致的,可以用置信区间检验实现区间检验的目的。     

谈谈两总体比较的非参数检验方法

针对不同的数据类型,探讨选用不同的非参数检验方法,并通过实例说明这些非参数检验方法的应用。     

A Comparison of Two-Sample Tests of Significance When Used With Variable Treatment Effects

This article compares the performance of many two-sample tests of significance that might be used to test the equality of means when the effect of the treatment is variable. Of the 19 tests that were compared, the normal scores test is recommended for general use in testing the null hypothesis of no treatment effect against the alternative that the distributions are stochastically ordered when the ratio of the larger standard deviation to the smaller standard deviation does not exceed 1.3. The Baumgartner-Weiß-Schindler tests and an adaptive test also have higher power than the pooled t-test, the unequal variance t-test, and the rank-sum test for many distributions. In the simulation studies, data in the first sample are generated from nine distributions, including long-tailed and skewed distributions. Data in the second sample are generated by adding a random treatment effect to a random variable that was generated from the same distribution that was used in the first sample. Because we restricted our power studies to treatment effects that are positive or zero, the population distributions will be stochastically ordered. The results of these studies demonstrate that the normal scores test is often more powerful than the t-tests and the rank-sum test. If the ratio of the standard deviations does exceed 1.3, then one of the t-tests is recommended.     

Testing equality of proportions for correlated binary data in ophthalmologic studies

In ophthalmologic studies, bilateral correlated data often arise when information involving paired organs (e.g., eyes) are measured from each subject. Adjusted chi-square approach for testing the equality of proportions has been proposed in the literature. In this article, we investigate and derive three alter- native testing procedures for the problem. Our simulation results show the score testing procedure usually produces satisfactory type I error control with higher power, and therefore is recommended. Examples from ophthalmologic studies are used to illustrate our proposed methods.     

中国药品上市后抽验模式现状及问题

目的在综合分析中国药品上市后抽验模式现状及问题的基础上,提出药品上市后抽验的建议。方法通过文献研究的方法,发现中国药品上市后抽验模式中存在的问题,并提出相关建议。结果与结论在药品抽验中引入以风险为基础的抽验模式,将药品上市后抽验结果与药品监管相衔接。     

Mutagenicity testing of quinine with submammalian and mammalian systems

Quinine hydrochloride was assayed for genotoxic activity by using 4 different test systems with distinct genetic endpoints. No indications for point mutations were observed in the Ames system. In 3 cytogenetic tests performed on small rodents, Chinese hamsters showed no genotoxic activity, while inbred strains of mice revealed a dose dependent increase of SCEs, enhanced incidence of micronuclei and elevated chromatid breaks.     

Simultaneous Test for Superiority and Noninferiority Hypotheses in Active-Controlled Clinical Trials∗

The primary objective of the dose-escalation trial for NGX267 was to estimate the maximally tolerated dose (MTD) and to gather detailed clinical and pharmacokinetic observations near the MTD. The MTD was defined based on the weighted average of moderate and severe adverse events. An adaptive design was employed to concentrate dosage assignments at or near the MTD. Favoring the acquisition of data near the MTD, at the expense of information at lower dosage levels, resulted in a shorter trial and no loss of the type of information required to inform subsequent studies where larger normal volunteer or patient samples are evaluated.     

刹毒草口服液的药理作用研究

目的:研究刹毒草口服液对小鼠的药理作用。方法:用小鼠分别进行爬杆实验、炭粒廓清实验、耳肿胀实验和墨汁推进实验,观察刹毒草口服液对小鼠的抗疲劳作用、非特异性免疫功能的影响、抗炎作用和抗腹泻作用。结果:刹毒草口服液能显著延长小鼠爬杆时间,有较好的抗疲劳作用;高剂量刹毒草口服液能显著提高小鼠对惰性炭粒的吞噬指数及吞噬活性,可提高小鼠免疫功能;刹毒草口服液3个剂量组均对二甲苯致小鼠耳炎症有较好的抑制作用,且能显著降低墨汁推进的速率,有较好的抗腹泻作用。结论:刹毒草口服液具有一定抗疲劳、抗炎、提高非特异性免疫功能和抗腹泻作用。     

氢溴酸山莨菪碱注射液细菌内毒素检查法的建立

目的:建立氢溴酸山莨菪碱注射液的细菌内毒素检查方法。方法:按《中国药典》2010年版(二部)附录相关方法确定本品细菌内毒素限值,分别进行细菌内毒素检查凝胶法和动态浊度法的干扰试验。结果:凝胶法结果表明,样品稀释2倍(5 mg/ml)时对试验无干扰作用;动态浊度法结果表明,本品稀释2倍(5 mg/ml)时外加内毒素的回收率在50%²00%之间。每1 mg氢溴酸山莨菪碱中含内毒素应小于0.35 EU。结论 :本文初步建立的氢溴酸山莨菪碱注射液细菌内毒素检查方法,可为《中国药典》增订该制剂的细菌内毒素检查项提供参考。     

Bootstrap inference in a linear equation estimated by instrumental variables

Summary We study several tests for the coefficient of the single right‐hand‐side endogenous variable in a linear equation estimated by instrumental variables. We show that writing all the test statistics—Student's t, Anderson–Rubin, the LM statistic of Kleibergen and Moreira (K), and likelihood ratio (LR)—as functions of six random quantities leads to a number of interesting results about the properties of the tests under weak‐instrument asymptotics. We then propose several new procedures for bootstrapping the three non‐exact test statistics and also a new conditional bootstrap version of the LR test. These use more efficient estimates of the parameters of the reduced‐form equation than existing procedures. When the best of these new procedures is used, both the K and conditional bootstrap LR tests have excellent performance under the null. However, power considerations suggest that the latter is probably the method of choice.