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利巴韦林注射液中间产品含量快速测定方法作者：肖七琪周其超张悦来源：《科技视界》 2013年第9期肖七琪周其超张悦（西南药业股份有限公司，中国重庆 400038）【摘要】目的：寻找简单快捷的方法测定利巴韦林注射液的含量。
方法：利用利巴韦林含有—OH、—NH2基团的化合物，为N—à跃进，从结构确定有紫外吸收，采用紫外分光光度法测定其含量。
结果：采用紫外分光光度法测定结果在206nm处的吸收度和含量呈良好的线性关系，标准曲线为：C=21.42A-0.5231，线性范围2～20μg/ml，RSD=0.59%。
结论：本法简便、准确，可用于利巴韦林注射液含量的测定。
【关键词】利巴韦林；氮测定法；紫外分光光度法利巴韦林注射液（1ml：100mg）是由利巴韦林和药用炭配制成的水溶性溶液。
利巴韦林是一种广谱抗病毒药，具有抑制呼吸道合胞病毒、流感病毒、甲肝病毒、腺病毒等多种病毒生长的作用。
在当前流感盛行的时期，利巴韦林注射液发挥了很大的作用。
为了保证药品质量，生产车间需对该药品实施中间产品监控，对产品含量、pH值和颜色进行测定，2010版《中国药典》规定利巴韦林注射液的检测方法为高效液相检测法。
由于高效液相色谱仪价格高昂，如果没购买该设备，就无法对中间产品实行质量控制，所以仍选用原有的氮测定法，而氮测定法方法操作较复杂，测定一份样需要1.5小时，由于利巴韦林注射液市场需求量大，而现在每晚2个批次投产，平行检测两次，需要6小时左右，无法满足生产需要，因此本研究拟探索一种通过紫外分光光度法，快速测定利巴韦林中间产品含量的新方法。
１仪器与试药UV—2401PC型紫外分光光度计（日本岛津），电子天平（sartotius）利巴韦林（广东肇庆星湖制药有限公司、10kg/桶、含量99.8%、原料批号L080102），注射用水（自制）。
2 试验方法2.1 溶液的制备2.1.1 对照品的制备精密称取利巴韦林对照品100mg，置100ml量瓶中，加水溶解并稀释至刻度，摇匀。
关于利巴韦林片含量测定方法改进分析【摘要】利巴韦林片属广谱抗病毒药。
适用于呼吸道合并病毒引起的病毒性肺炎与支气管炎，皮肤疱疹病毒感染。
常见的不良反应有贫血、乏力等，停药后即消失。
较少见的不良反应有疲倦、头痛、失眠、食欲减退、恶心、呕吐、轻度腹泻、便秘等，并可致红细胞、白细胞及血红蛋白下降。
【关键词】紫外分光光度法；高效液相色谱法；利巴韦林片doi：10.3969/j.issn.1004-7484（x）.2013.07.725文章编号：1004-7484（2013）-07-4101-021资料与方法1.1试验器材在此次试验中我们选择的实验器材是紫外分光光度仪，型号为mv-160ipc；高效液相色谱仪，型号为sp8800；电子天平，型号为ag245；用来测算时间及峰值的积分仪，型号为sp4400以及用来测试色谱柱状态变化的检测器，型号为sp100mv。
本次试验我们所选取的药品是：利巴韦林片，烧碱，以及水。
其中利巴韦林片要选择两种，分别用于试验与参照，烧碱的纯度要达到化学试剂二级纯度的标准，水的纯度也要达到超高的标准。
1.2试验方法1.2.1紫外分光光度法1.2.1.1测定波长的确定①用于试验的利巴韦林溶液的配制：从试验组里拿出二十片药物，并磨成细粉状，用电子天平量出其中的五十毫克，这里要注意精准度的把握，然后放进已准备好的带有刻度的容器当中。
之后选择浓度为每升0.01mol的烧碱，缓缓倒入装有利巴韦林粉末的容器中，直至溶液到达50毫升刻度线处。
最后将二者在容器内充分混合，得到试验所需的利巴韦林试验溶液，这时候的溶液浓度为每升1mg。
②用于参照的利巴韦林溶液的配制：这里需要提到的是参照组的利巴韦林片是经过高温烘干，处于恒重状态的。
将参照组的利巴韦林片磨成粉末状，用电子天平量出其中的五十毫克，这里要注意精准度的把握，然后放进已准备好的带有刻度的容器当中。
之后选择同样浓度的烧碱，采取同样的凡是倒入容器并将二者在容器内充分混合，从而得到我们参照所用的利巴韦林试验溶液，这时候的溶液浓度同样为每升1mg。
饲料和鸡肉中利巴韦林的测定--超高效液相色谱-串联质谱法刘凯;王丽娜;李建忠【摘要】本研究建立了饲料和鸡肉中利巴韦林的UPLC-MS/MS分析方法。
样品经三氯乙酸-乙腈溶液提取，离心后提取液经PBA固相萃取小柱净化，0.1 mol/L 甲酸水溶液溶解，进行UPLC-MS/MS分析。
结果显示，利巴韦林在10.0～500.0 g/L浓度范围内线性关系良好，r2=0.9991。
以浓缩饲料、配合饲料、预混料和鸡肉等为添加基质，其回收率在90.0%～114.5%，检出限为25.0 g/kg，定量限为50.0 g/kg。
表明本方法灵敏度高、专属性好、操作简单、结果可靠，可满足饲料和鸡肉中利巴韦林的分析检测。
%A method of Ultra Performance Liquid Chromatography-Tandem mass spectrometry(UPLC-MS/MS) for determination of ribavirin in feeds and chicken was developed. The drugs were extracted with acetonitrile/trichloroacetic acid from analyte, then cleaned up with PBA cartridges. The elu-ent was assayed by UPLC-MS/MS. The detection and quantification limits were 25.0 µg/kg and 50.0 µg/kg respectively. The average recoveries were 90.0%~114.5%. The real sample tests showed this meth-od can be used for the sensitive and accurate determination of ribavirin in feeds and chicken.【期刊名称】《现代畜牧兽医》【年(卷),期】2014(000)005【总页数】5页(P15-19)【关键词】利巴韦林;饲料;鸡肉;UPLC-MS/MS【作者】刘凯;王丽娜;李建忠【作者单位】辽宁省兽药饲料畜产品质量安全检测中心，辽宁沈阳 110016;辽宁省兽药饲料畜产品质量安全检测中心，辽宁沈阳 110016;安捷伦科技中国有限公司，北京 100102【正文语种】中文【中图分类】R927.2利巴韦林为广谱抗病毒药，体外具有抑制呼吸道合胞病毒、流感病毒、甲肝病毒、腺病毒等多种病毒生长的作用。
中兽药散剂中非法添加利巴韦林的检测方法研究崔成富;陈创华;林海丹;黄宝珠;邓国东【摘要】The determination method of ribavirin violated in the two veterinary traditional Chinese herb medicine powders including Qingwenbaidusan and Cangzhuxiangliansan was established. Preliminarily observed by microscope, the positive samples were determined by HPLC. The results showed that the standard curves for ribavirin were in good linearity within a concentration range of 1 - 150 μg/mL. The average recoveries for ribavirin at the addition in the two powders ranged from 91.74% to 98.50% with the RSD from 0.08% to 0.58%. The limit of quantification （LOQ） was 1 -2 mg/kg. This method was fast and accurate, and could be applied to determine ribavirin in the two veterinary traditional Chinese herb medicine powders.%建立了清瘟败毒散和苍术香连散两种中兽药散剂中违规添加利巴韦林的检测方法。
样品经显微检查法初筛，对阳性样品进行高效液相色谱定量分析。
AB SCIEX针对畜产品中利巴韦林和金刚烷的快速检测方案作者：暂无来源：《食品安全导刊》 2013年第3期□ 上海爱博才思分析仪器贸易有限公司供稿近日，国内某肉鸡生产企业爆出非法使用某些饲料添加剂事件，在肉鸡饲养中非法添加多种兽用药物。
众所周知，目前抗生素滥用状况比较突出。
而且食源性抗生素几乎百分之百来自于动物源性食品的摄入，如被曝光的利巴韦林和金刚烷。
目前，相关部门尚未发行针对利巴韦林和金刚烷胺在动物源食品中的检测技术方法和国家标准，所以在媒体报道鸡肉中检测出利巴韦林和金刚烷成分后，AB SCIEX公司亚太应用支持中心上海实验室迅速开发了以畜产品为基质的样品中利巴韦林和金刚烷的检测方法。
公司在最短的时间内开发出快速、准确、灵敏、高效的检测方法，并开设多场技术讲座，为用户提供详细的技术讲解和应用培训。
除此之外，还为用户提供β-内酰胺类，大环内酯类，磺胺类，四环素等多种抗生素的检测方法，为客户提供全套的技术支持。
实验内容1.仪器设备和试剂AB SCIEX公司5500 QTRAP系统配岛津UFLC液相，安捷伦公司Poroshell 120EC-C18，2.1mmx150mm，2.7μm色谱柱。
利巴韦林标准物质（纯品）、金刚烷标准物质（纯品）、乙腈（色谱纯）、三氯乙酸（分析纯）、去离子水（Millipor超纯水，电阻≥18.2MΩ?cm）。
2.色谱条件流动相A：含0.1%甲酸水溶液(含5mM甲酸铵)，流动相B：乙腈/水（v/v，95:5）溶液，流速、梯度洗脱见表1；柱温：40℃；进样量：10μL。
3.质谱条件(1)离子源参数电离模式为ESI+；碰撞气CAD设置6（Medium）；气帘气Curtain Gas设置30Psi；雾化气Gas1/Gas2设置60/60Psi；喷雾电压IS设置5500V；离子源温度TEM设置650℃。
(2)化合物参数化合物质谱参数见表2。
4.标准溶液的配制两种标准物质用乙腈稀释到1000mg/mL的标准储备液，将利巴韦林稀释为到0.2、0.5、1、2、5、10ng/mL，金刚烷稀释到0.05、0.1、0.2、0.5、1、2、5、10ng/mL的混合标准工作浓度。
长治市三宝生化药业有限公司编号SBB2.8.5.6利巴韦林注射液生产工艺验证方案长治市三宝生化药业有限公司方案制订签名日期方案会签签名日期生产技术部签名日期验证小组签名日期方案批准质量保证部日期目录1.概述`````````````````````````````````````````````````````````````````````````````````````````````````````````````````````````````4` 1.1.产品简述``````````````````````````````````````````````````````````````````````````````````````````````````````````````4 1.2.处方及依据``````````````````````````````````````````````````````````````````````````````````````````````````````````41.3.生产工艺流``````````````````````````````````````````````````````````````````````````````````````````````````````````5`2.验证目的````````````````````````````````````````````````````````````````````````````````````````````````````````````````````53.验证的范围```````````````````````````````````````````````````````````````````````````````````````````````````````````````64.验证各部门职责及组织结构```````````````````````````````````````````````````````````````````````````````65.验证准备````````````````````````````````````````````````````````````````````````````````````````````````````````````````````76.验证内容及实施``````````````````````````````````````````````````````````````````````````````````````````````````````8` 6.1.洗瓶工序````````````````````````````````````````````````````````````````````````````````````````````````````````````8 6.2.配制工序```````````````````````````````````````````````````````````````````````````````````````````````````````````12 6.3.灌封工序```````````````````````````````````````````````````````````````````````````````````````````````````````````15 6.4.灭菌工序```````````````````````````````````````````````````````````````````````````````````````````````````````````20 6.5.灯检工序```````````````````````````````````````````````````````````````````````````````````````````````````````````24 6.6.包装工序```````````````````````````````````````````````````````````````````````````````````````````````````````````266.7.成品检验结果``````````````````````````````````````````````````````````````````````````````````````````````````287.偏差分析``````````````````````````````````````````````````````````````````````````````````````````````````````````````````298.验证结论``````````````````````````````````````````````````````````````````````````````````````````````````````````````````299.附表````````````````````````````````````````````````````````````````````````````````````````````````````````````````````````````29 9.1. 设备一览表及生产能力```````````````````````````````````````````````````````````````````````````````30 9.2.设备性能验证确认及检查情况表```````````````````````````````````````````````````````````````31 9.3参加验证人员培训情况检查表````````````````````````````````````````````````````````````````````32 9.4.厂房与公用设施验证的确认和检查情况表`````````````````````````````````````````````34 9.5.空气净化系统、工艺用水系统验证的确认和检查情况表`````````````````35 9.6.计量器具检查情况表```````````````````````````````````````````````````````````````````````````````````````36 9.7.三批（按四批准备）验证使用的原料、辅料和安瓿供应商确认及检查情况表`````````````````````````````````````````````````````````````````````````````37 9.8.质量检验系统验证和准备情况表```````````````````````````````````````````````````````````````38 9.9.检验仪器检查情况表``````````````````````````````````````````````````````````````````````````````````````39 9.10检验试剂检查情况表````````````````````````````````````````````````````````````````````````````````````40 9.11质量监控点、监控内容、监控方法、监控频次表`````````````````````````````411.概述1.1.利巴韦林注射液（1ml：100mg）常温状态下是无色的澄明液体，属抗病毒药，用于呼吸道合胞病毒引起的病毒性肺炎与支气管炎。
利巴韦林检测标准拼音名：Libaweilin英文名：Ribavirin书页号：2000年版二部－301C8H12N4O5 244.21本品为1-β-D-呋喃核糖基-1H－1，2,4,-三氮唑-3-羧酰胺。
按干燥品计算，含C8H12N4O5 应为98.5％～101.5％。
【性状】本品为白色结晶性粉末；无臭，无味。
本品在水中易溶，在乙醇中微溶，在乙醚或氯仿中不溶。
比旋度取本品，精密称定，加水制成每1ml中含40mg的溶液，依法测定(附录ⅥE)，比旋度为-35.0°至-37.0°。
【鉴别】(1)取本品约0.1g，加水10ml使溶解，加氢氧化钠试液5ml，加热至沸，即发生氨臭，能使湿润的红色石蕊试纸变蓝色。
(2)在含量测定项下记录的色谱图中,供试品溶液的主峰保留时间应与利巴韦林对照品峰的保留时间一致。
(3)本品的红外光吸收图谱应与对照的图谱(光谱集22图)一致。
【检查】酸度取本品0.5g，加水25ml溶解后，依法测定（附录ⅥＨ），pH值应为4.0～6.5。
吸收度取本品1.0g，加水25ml溶解后，照分光光度法（附录ⅣＡ），在430nm的波长处测定吸收度，不得大于0.02。
有关物质取本品，加水分别制成每1ml中含0.4mg的供试品溶液与每1ml中含5μg的对照溶液。
照含量测定项下的方法，取对照溶液10μl注入液相色谱仪进行预试，调整检测灵敏度，使主成分色谱峰高度达满量程的20％～25％；再取供试品溶液10μl注入液相色谱仪,记录色谱图至主峰保留时间的两倍,计算各杂质峰面积的和,不得大于总峰面积的1.0％。
干燥失重取本品，在105℃干燥至恒重，减失重量不得过0.5％（附录ⅧＬ）。
炽灼残渣取本品1.0g，依法检查（附录ⅧＮ），遗留残渣不得过0.1％。
重金属取炽灼残渣项下遗留的残渣，依法检查（附录ⅧＨ第二法），含重金属不得过百万分之十。
【含量测定】照高效液相色谱法（附录ⅤＤ）测定。
色谱条件与系统适用性试验用十八烷基硅烷键合硅胶为填充剂；以水或0.03mol/L硫酸铵溶液为流动相；检测波长为207nm。
利巴韦林工艺验证利巴韦林注射液生产工艺验证方案长治市三宝生化药业有限公司方案制订签名日期方案会签签名日期生产技术部签名日期验证小组签名日期方案批准质量保证部日期目录1.概述``````````````````````````````````````````````````````````````````````````````````` ``````````````````````````````````````````4``````````````````````````````````````41.2.处方及依据``````````````````````````````````````````````````````````````````````` ```````````````````````````````````41.3.生产工艺流``````````````````````````````````````````````````````````````````````` ```````````````````````````````````5`2.验证目的````````````````````````````````````````````````````````````````````````````` ```````````````````````````````````````53.验证的范畴`````````````````````````````````````````````````````````````````````````` `````````````````````````````````````64.验证各部门职责及组织结构```````````````````````````````````````````````````` ```````````````````````````65.验证预备````````````````````````````````````````````````````````````````````````````` ```````````````````````````````````````76.验证内容及实施``````````````````````````````````````````````````````````````````` ```````````````````````````````````8`6.1.洗瓶工序````````````````````````````````````````````````````````````````````````` ```````````````````````````````````86.2.配制工序````````````````````````````````````````````````````````````````````````` ``````````````````````````````````126.3.灌封工序````````````````````````````````````````````````````````````````````````` ``````````````````````````````````156.4.灭菌工序````````````````````````````````````````````````````````````````````````` ``````````````````````````````````206.5.灯检工序````````````````````````````````````````````````````````````````````````` ``````````````````````````````````246.6.包装工序````````````````````````````````````````````````````````````````````````` ``````````````````````````````````26```````````````````````````````287.偏差分析````````````````````````````````````````````````````````````````````````````` `````````````````````````````````````298.验证结论````````````````````````````````````````````````````````````````````````````` `````````````````````````````````````299.附表``````````````````````````````````````````````````````````````````````````````````` `````````````````````````````````````````299.1. 设备一览表及生产能力````````````````````````````````````````````````````` ``````````````````````````309.2.设备性能验证确认及检查情形表``````````````````````````````````````````` ````````````````````319.3参加验证人员培训情形检查表`````````````````````````````````````````````` ``````````````````````329.4.厂房与公用设施验证的确认和检查情形表``````````````````````````````` ``````````````349.5.空气净化系统、工艺用水系统验证的确认和检查情形表````````````` ````359.6.计量器具检查情形表`````````````````````````````````````````````````````````` `````````````````````````````369.7.三批（按四批预备）验证使用的原料、辅料和安瓿供应商确认及检查情形表```````````````````````````````````````````````````` `````````````````````````379.8.质量检验系统验证和预备情形表``````````````````````````````````````````` ````````````````````389.9.检验仪器检查情形表`````````````````````````````````````````````````````````` ````````````````````````````399.10检验试剂检查情形表````````````````````````````````````````````````````````` ```````````````````````````409.11质量监控点、监控内容、监控方法、监控频次表````````````````````` ````````411.概述1.1.利巴韦林注射液（1ml：100mg）常温状态下是无色的澄明液体，属抗病毒药，用于呼吸道合胞病毒引起的病毒性肺炎与支气管炎。
正式名：利巴韦林胶囊汉语拼音：Libaweilin Jiaonang标准号：WS-090（X-077）-94拉丁文或英文：Ribavirin Capsules主要活性成分：含利巴韦林（C8H12N4O5）性状：胶囊，内容物白色颗粒鉴别：（1）取本品内容物适量（约相当于利巴韦林0.1g），加水10ml，振摇使利巴韦林溶解，加氢氧化钠试液5ml，加热煮沸，即发生氨臭，并使湿润的红色石蕊试纸变为蓝色。
（2）取本品内容物适量（约相当于利巴韦林0.1 g），加水5ml，振摇使利巴韦林溶解，滤过，滤液加硫酸（1→2）3ml，置水浴中加热30分钟，放冷，加氢氧化钠试液中和，将此溶液分为三份，份加2.4-二硝基苯肼试液2ml，即生成桔红色沉淀；一份加氨制硝酸银试液2ml，即生成白色絮状沉淀，一份加碱性酒石酸铜试液5ml，加热，煮沸2分钟，即生成砖红色沉淀。
（3）取本品内容物适量（约相当于利巴韦林50m g），加水5ml，振摇使利巴韦林溶解，滤过，取滤液作供试品溶液；另取利巴韦林适量，加水制成每1ml中含10mg的溶液，作为对照溶液。
照薄层色谱法（中国药典1990年版二部附录30页）试验，吸取上述两溶液各10μl，分别点于同一硅胶G薄层板上，以醋酸乙酯-乙醇（1∶1）为展开剂，展开后，晾干，喷以硫酸，在110℃加热15分钟，立即检视。
供试品溶液所显主斑点的颜色和位置应与对照溶液的主斑点相同。
检查：溶出度取本品，照溶出度测定法（中国药典1990年版二部附录60页第一法），以水900ml 为溶剂，转速为每分钟50转，依法操作，经20分钟时，取溶液滤过，取续滤液5ml，用水稀释至100ml，照分光光度法（中国药典1990年版二部附录24页），在206nm的波长处测定吸收度；另取利巴韦林对照品适量，用水溶解并定量稀释制成每1ml中约含8μg的溶液，同法测定吸收度，计算出每粒的溶出量。
限度为标示量的90%，应符合规定。
其它应符合胶囊剂项下有关的各项规定（中国药典1990年版二部附录8页）。
1.目的：指导检验人员掌握正确的操作方法，以确保检测结果的准确性和可靠性。
2.适用范围：仅适用于本公司。
3.责任：质量控制部经理、化验室主任、化验员。
4.标准依据：利巴韦林内控质量标准5.内容：5.1.【性状】5.1.1.标准规定：本品为白色或类白色结晶性粉末；无臭，无味。
5.1.1.1.仪器：偏光显微镜，载玻片5.1.1.2.试液：液状石蜡5.1.1.3.操作方法：取本品少许，置载玻片上，加液状石蜡1滴使悬浮，在偏光显微镜下检视。
观察转动载物台时，是否呈现消光位和双折射现象，进行结晶性判断。
5.1.1.4.结果与判定：根据所观察的供试品外观与转动载物台时，是否呈现消光位和双折射现象进行判断，与上述描述相符者，判为结晶性粉末。
5.1.2.标准规定：本品在水中易溶，在乙醇中微溶，在乙醚或二氯甲烷中不溶。
5.1.2.1.用具：小试管5.1.2.2.试剂：乙醚、乙醇、二氯甲烷5.1.2.3.操作方法：称取研成细粉的供试品，置于25℃±2℃一定容量的溶剂中，每隔5分钟强力振摇30秒钟；观察30分钟内的溶解情况，如无目视可见的溶质颗粒时，即视为完全溶解。
5.1.2.4.结果与判定：本品在水中易溶，在乙醇中微溶，在乙醚或二氯甲烷中不溶，判为符合规定；否则，判为不符合规定。
5.1.3.比旋度5.1.3.1.标准规定：40mg/ml的水溶液比旋度为-35.0o至－37.0o。
5.1.3.2.仪器与用具：分析天平、旋光仪、温度计5.1.3.3.操作方法5.1.3.3.1.取本品2.0g，精密称定，置50ml容量瓶中，加水稀释至刻度，制成每1ml中约含40mg的溶液，摇匀，使供试品溶液的温度控制在20℃±0.5℃。
用空白溶剂校正仪器零点，供试品溶液与空白溶液同一测定管，每次测定应保持测定管方向，位置不变，按比旋度测定法SOP测定，记录所测数据，旋光度读数应重复3次，取其平均值。
5.1.3.4.计算公式：[α]t D=100×αL×C=α×V样2×W样×(1-干燥失重%)式中:[α]为比旋度α为测定的旋光度L为测定管的长度，dmW为供试品重量，g5.1.3.5.结果与判定：计算所得数值按有效数字修约规则修约为标准规定的有效数字，若此数在-35.0o至－37.0o。
范围内，判为符合规定；否则，判为不符合规定。
5.1.3.6.注意事项：供试品溶液配制后应及时测定；通电开机之前应取出仪器样品室内的物品。
开机预热约20分钟后再进去测定。
测定时注意环境温度。
5.2.【鉴别】5.2.1.（1）5.2.1.1.试剂与试液：氢氧化钠试液、5.2.1.2.操作方法：取本品约0.1g，加水10ml使溶解，加氢氧化钠试液5ml，加热至沸，即发生氨臭，能使湿润的红色石蕊试纸变蓝色。
5.2.1.3.结果与判定：若变蓝色，判为符合规定；否则，判为不符合规定。
5.2.2.（2）5.2.2.1.标准规定：在含量测定项下记录的色谱图中，供试品溶液主峰的保留时间应与对照溶液主峰的保留时间一致。
5.2.2.2.操作方法：参见含量测定项下所得的色谱数据，对供试品溶液的主峰保留时间与利巴韦林对照品溶液主峰的保留时间进行比较。
5.2.2.3.结果与判定：若二者的保留时间一致，判为符合规定；否则，判为不符合规定。
5.2.3.（3）5.2.3.1.仪器：红外分光光度计5.2.3.2.操作方法：取本品红外光谱测定SOP测定本品的红外光吸收图谱，核对本品的红外光吸收图谱与对照的图谱（光谱集22图）是否一致。
5.2.3.3.结果与判定：若二者一致，判为符合规定；否则，判为不符合规定。
5.3.【检查】5.3.1.酸度5.3.1.1.仪器：分析天平、酸度计5.3.1.2.试剂与试液：饱和氯化钾溶液5.3.1.3.操作方法5.3.1.3.1.选择用pH值为6.86的磷酸盐缓冲液进行校正（定位），再用pH值为4.01的苯二甲酸盐标准缓冲液进行核对。
5.3.1.3.2.取本品约1.0g ，置100ml烧杯中，加新沸放冷的纯化水50ml溶解后，加饱和氯化钾溶液0.2ml，摇匀；测定时用供试液淋洗电极数次，将电极浸人供试液中，轻摇供试液平衡稳定后，进行读数。
5.3.1.4.结果与判定：若pH值为4.3～6.2，判为符合规定；否则，判为不符合规定。
5.3.1.5.注意事项：标准缓冲液如发现有浑浊、发霉或沉淀等现象，不能继续使用。
5.3.2.溶液澄清度与颜色5.3.2.1.仪器与用具：分析天平、紫外-可见分光光度计、澄明度检测仪、纳氏比色管5.3.2.2.试剂与试液：0.5号～1号浊度标准液、黄色或黄绿色1号标准比色液5.3.2.2.1.浊度标准贮备液的制备：称取于105℃干燥至恒重的硫酸肼1.00g，置100ml量瓶中，加水适量使溶解，必要时可在40℃的水浴中温热溶解,并用水稀释至刻度，摇匀，放置4～6h；取此溶液与等容量的10%乌洛托品溶液混合，摇匀，于25℃避光静置24h，即得。
本液置冷处避光保存，可在两个月内使用，用前摇匀。
5.3.2.2.2.浊度标准原液的制备：取浊度标准贮备液15.0ml，置1000ml量瓶中，加水稀释至刻度，摇匀，取适量、置lcm吸收池中，照紫外-可见分光光度法(SOP)在550nm的波长处测定，其吸光度应在0.12 ～0.15范围内。
本液应在48h内使用，用前摇匀。
5.3.2.2.3.浊度标准液的制备：取浊度标准原液2.5ml与水97.5ml混合均匀制成0.5号浊度标准液，取浊度标准原液5.0ml与水95.0ml混合均匀制成1号浊度标准液，本液应临用新制，用前摇匀。
5.3.2.3.操作方法：取本品0.5g，加水10ml溶解后，溶液应澄清无色；如显浑浊，与1号浊度标准液比较；如显色，与黄色或黄绿色1号标准比色液。
5.3.2.4.结果判定：若供试品溶液的浊度浅于或等于0.5号的浊度标准液且颜色同于水，即为澄清无色；如浊度浅于或等于1号浊度标准液，显色浅于或等于黄色或黄绿色1号标准比色液，判为符合规定；否则，判为不符合规定。
5.3.3.有关物质5.3.3.1.仪器：分析天平、高效液相色谱仪5.3.3.2.色谱条件与系统适用性试验照含量测定项下的色谱条件5.3.3.3.溶液的制备5.3.3.3.1.供试品溶液的制备：取本品约40mg，精密称定，置100ml量瓶中，加流动相制成每1ml中含0.4mg的溶液，作为供试品溶液。
5.3.3.3.2.对照溶液的制备：精密量取供试品溶液1.0ml，置100ml量瓶中，用流动相稀释至刻度，摇匀，作为对照溶液。
5.3.3.4.测定法：取对照溶液各20μl，注入液相色谱仪，调节仪器灵敏度，使主成分峰的峰高为满量程的25%；再精密量取供试品溶液与对照溶液各20μl，分别注入液相色谱仪，记录色谱图至主成分峰保留时间的2倍。
5.3.3.5.结果与判定：供试品溶液的色谱图中如有杂质，单个杂质的峰面积不得大于对照溶液峰面积的0.25倍（0.25%），各杂质峰面积的和不得大于对照品溶液的主峰面积的0.8倍（0.8%）。
5.3.4.干燥失重5.3.4.1.仪器与用具：分析天平、鼓风干燥箱、扁形称量瓶5.3.4.2.操作方法：取本品1.0g，精密称定，置105℃干燥至恒重的空扁形称量瓶中，在105℃干燥至恒重。
5.3.4.3.计算公式：干燥失重%=W1-W2W1-W瓶×100%式中：W1为干燥前空称量瓶与供试品的总重量（g）W2为干燥后空称量瓶与供试品的总重量（g）W瓶为空称量瓶干燥恒重的重量（g）5.3.4.4.结果与判定：计算所得数字根据有效数字的修约规则进舍小数点后一位数字，此数若小于或等于0.5%，判为符合规定；否则，判为不符合规定。
5.3.5.炽灼残渣5.3.5.1.仪器与用具：分析天平、高温炉、电炉、坩埚长柄坩埚钳、干燥器5.3.5.2.试剂：硫酸。
5.3.5.3.操作方法：取本品1.0g，精密称定，按炽灼残渣检查SOP检查，记录所称量数据。
5.3.5.4.计算公式遗留残渣%=炽灼后埚和残渣重－炽灼前空埚重供试品取用量×100%5.3.5.5.结果与判定：以上计算数值修约成1位有效数字，若此数小于或等于0.1%，判为符合规定；否则，判为不符合规定。
5.3.6.重金属5.3.6.1.标准规定：含重金属不得过百万分之十5.3.6.2.仪器与用具：分析天平、25ml纳氏比色管、移液管5.3.6.3.试剂与试液：标准铅溶液（10μg/ml）、硫代乙酰胺试液、醋酸盐缓冲液（pH3.5）、硝酸、盐酸、氨试液、酚酞指示液5.3.6.4.操作方法5.3.6.4.1.甲管：取标准铅溶液1.0ml，置坩埚中，加硝酸0.5ml，蒸干，至氧化氮蒸气除尽后，放冷，加盐酸2ml,置水浴上蒸干后加水15ml,滴加氨试液至对酚酞指示液显微粉红色，再加醋酸盐缓冲液（pH3.5)2ml,微热溶解后，移至25ml纳氏比色管中，加水稀释成25ml；5.3.6.4.2.乙管：取炽灼残渣项下遗留的残渣，加硝酸0.5ml，蒸干，至氧化氮蒸气除尽后，放冷，加盐酸2ml,置水浴上蒸干后加水15ml,滴加氨试液至对酚酞指示液显微粉红色，再加醋酸盐缓冲液（pH3.5)2ml,微热溶解后，移至25ml纳氏比色管中，加水稀释成25ml，作为样品管；5.3.6.4.3.在甲、乙两管中分别加硫代乙酰胺试液各2ml，摇匀，放置2分钟，同置白纸上，自上向下透视。
5.3.6.5.结果与判定：若乙管所显颜色浅于或等于甲管所显颜色，判为符合规定；否则，判为不符合规定。
5.4.【含量测定】5.4.1.仪器：分析天平、高效液相色谱仪5.4.2.试剂、试液与对照品：稀硫酸、利巴韦林对照品5.4.3.色谱条件与系统适用性试验用磺化交联的苯乙烯-二乙烯基共聚物的氢型阳离子交换树脂为填充剂；以水（用稀硫酸调节pH值至2.5±0.1）为流动相；检测波长为207nm。
理论板数按利巴韦林峰计算不低于2000。
5.4.4.溶液的制备5.4.4.1.供试品溶液的制备：取本品约25mg，精密称定，置50ml容量瓶中，加流动相溶解并稀释至刻度，摇匀，精密量取5.0ml，置50ml容量瓶中，加流动相溶解并稀释至刻度，摇匀，作为供试品溶液。
5.4.4.2.对照溶液配制：取利巴韦林对照品约25mg，精密称定，置50ml容量瓶中，加流动相溶解并稀释至刻度，摇匀，精密量取5.0ml，置50ml容量瓶中，加流动相溶解并稀释至刻度，摇匀，作为对照品溶液。
5.4.5.测定法：精密量取供试品溶液与对照品溶液各20μl，注入液相色谱仪，记录色谱图，供试品溶液如出现于对照品溶液相应的峰，按外标法以峰面积计算。
