欧洲药典疑难问答
在EDQM的官网FAQ and HelpDesk专栏上挂出关于欧洲药典总论和各论的解答，摘录了一些内容和网上的翻译，供大家参考。
07. If I analyse a substance according to a Ph. Eur. monograph, do I also need to demonstrate compliance with the national monograph?
如果我按照欧洲药典各论对物质进行了分析，我还需要证明符合国家各论吗？
No. The European Pharmacopoeia monographs are valid in all the Member States of the European Pharmacopoeia.
不需要。欧洲药典各论在欧洲药典所有成员国内均有效。
08. If I analyse a substance according to a national monograph, do I also need to demonstrate compliance with a Ph. Eur. monograph?
如果我按照一个国家各论对物质进行了分析，我还需要证明其符合欧洲药典各论吗？
This question should be addressed to the competent authorities of the countries involved. As a minimum, for Ph. Eur. Member states, you should ensure that the European Pharmacopoeia monograph has been transposed into the national pharmacopoeia by the specified implementation date
这个问题需要向相关国家的管理机构咨询。最低要求，对于欧洲药典成员国，你必须保证欧洲药典各论已在指定的实施日期引入了国家药典。
14. Do I need to validate a method that is published in the Ph. Eur.?
我是否需要验证欧洲药典里公布的分析方法？
The test methods given in monographs and general chapters have been validated in accordance with accepted scientific practice and current recommendations on analytical validation. Unless otherwise stated in the monograph or general chapter, validation of the test methods by the analyst is not required. When implementing a pharmacopoeial method, the user must assess whether and to what extent the suitability of the method under the actual conditions of use needs to be demonstrated according to relevant monographs, general chapters and quality systems, i. e. the correct method transfer is the responsibility of the user.
在各论和通则里给定的分析方法已经过验证，符合可接受的科学规范和分析方法验证现行建议。除非在各论或通则里另有规定，化验员不需要进行方法验证。在实施药典方法时，用户必须评估方法的在实际使用条件下的适用程度，需要根据相关的各论、通则和质量体系进行证明，也就是说，用户有义务保证方法正确转移。
17. For how long can I store a reagent or a solution before using it?
试剂和溶液在使用之前我可以存贮多久？
Unless prescribed in the monograph, the Ph. Eur. does not define expiry dates for the use of reagents or solutions. It is the responsibility of the user to determine their shelf-life.
除非各论里有规定，否则EP并不定义试剂和溶液的使用有效期。用户有义务确定其保存时间。
18. Can I use a reagent or method other than the on
The tests and assays described are the official methods upon which the standards of the Pharmacopoeia are based. With the agreement of the competent authority, alternative methods of analysis may be used for control purposes, provided that the methods used enable an unequivocal decision to be made as to whether compliance with the standards of the monographs would be achieved if the official methods were used (cross-validation). In the event of doubt or
dispute, the methods of analysis of the Pharmacopoeia are alone authoritative. It is not the role of the EDQM to approve alternative methods or reagents.
所述的测试和方法是官方方法，药典以此为标准。在相关药监机构同意的情况下，可以使用替代分析方法来控制，所使用的方法必须能够清楚地证明如果使用官方方法时是否能达到各论标准（交叉验证）。如果有疑问或争议，则只有药典分析方法是权威的。EDQM没有职责来批准替代方法或试剂。
20. How can I standardise a volumetric solution?
我是否能够标定滴定液？
Volumetric solutions are standardised by the methods described in chapter 4.2.2. When a volumetric solution is to be used in an assay in which the end-point is determined by an electrochemical process (for example, amperometry or potentiometry) the solution is standardised by the same method. The composition of the medium in which a volumetric solution is standardised should be the same as that in which it is to be used.
滴定液应采用第4.2.2章所述方法标定。如果一个滴定液将用于检测，检测由电子化学过程来判定终点（例如，安培法或电位法），则应将溶液采用相同方法标化。滴定液标化所用的介质组份应与检测所用的相同。
23 I have observed a slight difference in retention times/retardation factors compared with the monograph. What deviation is considered acceptable?
我发现相比于各论，保留时间/延迟因子有些许差异。什么样的偏差是可以接受的呢？
The retention times, relative retentions and retardation factors are normally not part of the system suitability criteria; they are given for information on
保留时间、相对保留时间和拖尾因子一般并不是系统适用性标准的一部分，他们是仅供参考的信息，并不是强制的要求。因此，并没有定义偏差允许程度。不管怎样，必须符合各论里给定的系统适用性要求，才可以继续检测。
24 What is the limit for specified/unspecified/unknown impurities?
已知/未识别/未知杂质的限度是什么？
Unless otherwise prescribed or justified and authorised, organic impurities in active substances are to be reported, identified wherever possible, and qualified as indicated in general monograph 2034, Substances for pharmaceutical use (Table 2034.-1 or Table 2034.-2).
除另有规定或者判定和授权外，原料药里的有机杂质要按通论2034“药用物质”（表2034-1或表2034-2）的要求进行报告、可能时鉴定，并定性。
Generally, specified impurities have their own specific acceptance criterion in the monograph. For other impurities, the decision tree in general chapter 5.10, Control of impurities in substances for pharmaceutical use may be used to determine the applicable acceptance criterion.
一般来说，在各论中已知杂质具有其自身特定的可接受标准。对于其它杂质，可以使用通则5.10“药用物质中杂质控制”的决策树来确定适用的可接受标准。
25 How to determine the total impurities? Which peaks can be disregarded?
如何确定总杂质？哪些峰可以忽略？
In chromatographic tests, the disregard limit is defined as the nominal content at or below which peaks/signals are not taken into account for calculating a sum of impurities. The numerical values for the disregard limit and the reporting threshold are usually the same.
在色谱测试中，忽略限定义为等于或低于不需要计入杂质总计的峰/信号的名义含量。忽略限和报告阈的数值通常是相同的。
Peaks corresponding to the blank can also be disregarded, as well as other peaks that the monograph explicitly states are to be disregarded.
与空白相对应的峰，以及各论明确声明可以忽略的峰也可以忽略。
In other words, if impurities (specified or unspecified) are above the disregard limit, they should be taken into account for the calculation of the total impurities.
换句话说，如果杂质（已知或未鉴定杂质）超出忽略限，则在计算总杂时要考虑进去。
26 The limit for unspecified impurities in the monograph is higher than the values defined in general monograph 2034, Substances for pharmaceutical use (Table 2034.-1) and general chapter 5.10, Control of impurities in substances for pharmaceutical use.
各论里未鉴定的杂质限度高于通论2034“药用物质”（表2034-1）和通则5.10“药用物质里杂质控制”里定义的值。
Some monographs are awaiting revision. However, the requirements of the general monograph are binding and must be implemented by the user as described in general chapter 5.10. In some exceptional cases, the requirements of general monograph 2034 and general chapter 5.10 do not apply, and different thresholds can be prescribed. In this case, the following statement can be found in the related substances section: “The thresholds indicated under Related substances (Table 2034.-1) in the general monograph Substances for Pharmaceutical use (2034) do not apply”.
一些各论等待修订。但是，通论里的要求是强制的，用户必须符合通则5.10里的要求。在一些例外情形下，通论2034和通则5.10的要求不适用，可以制订不同的阈值。在此情形下，在相关物质部门可以找到以下声明“不适用通论药用物质中在相关物质项下给定的阈值（表2034-1）”。
28 I observe baseline separation when the monograph describes a peak-to-valley ratio.
我这里是基线分离度，但各论描述的是峰谷比。
Even though a peak-to-valley ratio cannot be calculated in this case, the requirement is fulfilled as the separation is even better than what the monograph prescribes.
即使在此情形下不能计算峰谷比，还是满足要求的，因为分离度比起各论所述的更好。
29 I cannot achieve the system suitability or signal-to-noise criteria with the described chromatographic method. Can I make any adjustments?
我不能达到色谱方法里所述的系统适用性或信噪比标准，我能做出调整吗？
Please consult General Chapter 2.2.46, section “Adjustment of chromatographic conditions” for a list of acceptable modifications. However, multiple modifications are not recommended, and in any case, the system suitability criteria of the monograph and of chapter 2.2.46 must be met.
请参考通则2.2.46章“色谱条件调整”部分里的可接受修订清单。但是，并不建议做多个修订，不管怎样，必须符合各论中的系统适用性标准和通则2.2.46的要求。
30. The monograph does not specify a correction factor for a specified impurity.
各论并未指定特定杂质的校正因子。
If the monograph does not describe a correction factor, it is assumed that it is in the range between 0.8 and 1.2 and therefore you do not need to apply a correction factor to this impurity.
如果各论中并未给定校正因子，则假定其在0.8-1.2的范围，因此你不需要对此杂质采用校正因子进行计算。
31. The monograph does not include chemical reference substances or relative retentions for specified impurities.
各论并未包括特定杂质的化学对照物质或相对保留时间。
This monograph might be part of our revision programme to introduce chemical reference substances for peak identification and relative retentions for specified impurities as well as an explicit acceptance criterion for unspecified impurities. Please contact us if you can submit further information.
此各论可能是我们修订计划的一部分。我们将会进行修订引入化学对照物质用于峰鉴别，以及确定特定杂质的相对保留时间，并为非特定杂质制订清楚的可接受标准。如果你能够提交更多资料，请与我们联系。
32. What is the difference between a peak area comparison and a quantitative limit for related substances?
相关物质峰面积比较和定量限度有什么区别？
In the past, the acceptance criteria for related substances were expressed relative to the area of a reference peak of known concentration (limit test). Without providing a numerical result, the comparison of peak areas leads to a pass/fail decision. For comparative tests, the approximate content of impurity tolerated, or the sum of impurities, is indicated in brackets for information on
most cases, current monographs describe quantitative determinations: a
calculation of the content is necessary to establish compliance with the
monograph.
在过去，有关物质的可接受标准表述为与已知浓度（限度测试）的对照峰面积进行比较的结果。由于不能提供数值式结果，峰面积比较只能得到合格/不合格的结果。在对比测试中，允许的大致杂质含量，或者是杂质合计，在括号里给出仅供参考。在大多数情形下，目前的各论描述的是定量检测，需要对含量进行计算以确定是否符合各论要求。
33. In the case of a harmonised monograph, is it possible to use a reference standard from a different pharmacopoeia?
如果各论是协调过的，是否有可能使用不同药典的对照标准？
No. The use of a European Pharmacopoeia monograph requires the use of European Pharmacopoeia reference standards that are reviewed and approved by the European Pharmacopoeia Commission.
不可以。使用EP各论就要求使用经过EP委员会审核和批准的EP对照品。
34. Is it possible to perform a type of measurement (such as ATR) different from that described in the monograph?
是否可能实施与各论不同的检测（例如ATR）？
In principle, you can choose on
原则上来说，你可以选择2.2.24章里的一种方法，除非各论描述了与对照图谱比较，或者清楚说明了制备方法。否则，需要与各论进行交叉验证。不管如何，你必须对待测物质在相同的条件下使用相同的程序和标准。
35. Do I have to perform all the tests described in the Identification section of a monograph?
我是否必须做各论中鉴别部分所述的所有鉴别测试？
No, the test or tests that constitute the ‘First identification’ may be used in all circumstances. The second identification series is not intended for use in any other context than pharmacies. It may be used on
不需要。在所有情形下，都可以只做“第一鉴别”中所包括的测试。第二鉴别系列是为了药房设计的，其它情况下不需要做。如果可以证明物制或制剂可以追踪至经过认证符合各论所有其它要求的批次，它才会被使用。
36. I have trouble meeting the criteria under “Characters”.
我没法符合“性状项”下的标准。
The statements under the heading Characters are not to be interpreted in a strict sense and are not requirements. It is therefore not mandatory to verify compliance with the Characters section for batch release.
在“性状”项下的声明并不是严格诠释的，也不是要求。因此，在批放行时并不强制要求确认与性状部分的要求相符合。
37 Which is the difference between “dried” and “anhydrous” substance?
“干燥”和“无水”物质之间有什么区别？
“Dried substance” takes into account the loss on drying test (including class 3 solvents), whereas “anhydrous substance” refers to the result obtained by the water determination. It is imp
of the assay content of the substance, the specific optical rotation and the specific absorbance, even if not explicitly stated in the definition.
“干品”考虑的是干燥失重测试（包括3类溶液），而“无水物”指的是通过水分检测得到的结果。重要的一点是需要注意，当对物质的残留溶剂进行定量测定，并且没有测定LOD时，物质含量、比旋、吸光的计算中要考虑残留溶剂的含量，即使在定义没有清楚说明，也是要考虑的。
38 The definition of substance X gives the content on dried or anhydrous basis. What about the solvents, are they to be taken into account when determining the assay?
物质X的定义中说含量是以干品计或以无水物计。那溶剂呢，在计算含量时也要考虑吗？
In accordance with the general monograph Substances for pharmaceutical use (2034), the content of residual solvents is taken into account for calculation of the assay content of the substance, the specific optical rotation and the specific absorbance. This information is therefore not indicated in the specific monographs concerned.
根据药用物质通论（2034），在计算物质含量、比旋和吸光时要考虑残留溶剂的含量。因此，在各论中并没有特意说明此要求。
39. What precision is required for weighing or measuring?
称重和测量时，要求的精确度是怎样的？
In tests with numerical limits and assays, the quantity stated to be taken for examination is approximate. The amount actually used, which may deviate by not more than 10 percent from that stated, is accurately weighed or measured and the result is calculated from this exact quantity.
在数值限度和含量测试中，检测用数量为大约。实际所用的数量可以与所要求的数量差异10%以内，要准确称重或测量，结果要采用确切的数量来计算。
In tests where the limit is not numerical, but usually based on comparison with the behaviour of a reference substance under the same conditions, the stated quantity is taken for examination.
在非数值式限度测试中，通常是基于与对照物质在相同条件下相比较的情形下，则应取用所指明的检测用数量。
Reagents are used in the prescribed amounts.
所用的试剂应按所述数量取用。
For weighing, the precision corresponds to plus or minus 5 units after the last figure stated (for example, 0.25 g is to be interpreted as 0.245 g to 0.255 g).
如果是称重，应称取指定数值的最后一位之后±5个单位（例如，0.25g应称量0.245g-0.255g）的重量。
40. Am I allowed to round off measurements?
是否允许修约结果？
In determining compliance with a numerical limit, the calculated result of a test or assay is first rounded off to the number of significant figures stated, unless otherwise prescribed. The limits, regardless of whether the values are expressed as percentages or as absolute values, are considered significant to the last digit shown (for example, 140 indicates 3 significant figures). The last figure of the result is increased by on
half-unit.
在确定数值式限度是否符合标准之前，测试或含量计算所得结果应先修约至所要求的有效数值，另有说明者除外。限度值，不管是否表达为百分比还是绝对数值，都认为其所显示的最后一位是有效的（例如，140为3位有效数值）。当被修约的位数字等于或大于一半单位时，结果的最后一位数加1，当被修约的数字位小于一半单位时，结果的最后一位数不变。
41. In chapter 2.5.12, how do I proceed if the water content of my sample is below 2.5 mg?
在2.5.12章中，如果我的样品里水含量小于2.5mg，我要怎么往下做呢？
The method described in chapter 2.5.12 is suitable for water contents between 2.5 and 25 mg. If your sample contains less than 2.5 mg of water, you can add a known amount of water so that the total amount of water is within the indicated limits. If you decide to use the micro-determination 2.5.32, this would be regarded as an alternative method and it would have to be cross-validated accordingly, unless it is described in the monograph.
在第2.5.12章里所述的方法适用于水分含量在2.5至25mg之间。如果你的样品含水低于2.5mg，你可以增加已知数量的水，让水的总数量在所指的限度内。如果你决定使用微量测定法2.5.32，则会被当作是替代方法，必须相应地做交叉验证，各论里另有描述者除外。
42. In chapter 2.5.12, what solvent should I use for the water determination?
在2.5.12章中，在测定水时我要用什么溶剂？
Use the solvent indicated in the monograph or recommended in the Knowledge database. Alternatively, methanol R or the solvent recommended by the supplier of the titrant may be used, provided that the suitability requirements are fulfilled.
使用各论中所给定的溶剂，或者在知识数据库里推荐的溶剂。如果满足适用性要求的话，也可以使用试剂级甲醇，或者供应商推荐的溶剂。
45. Does the suitability test described in chapter 2.5.12 have to be run every time?
在第2.5.12中所述的适用性测试是否每次都要做？
The suitability test has to be carried out on
适用性测试只要做一次，就是在将商业滴定剂和待测物质联合应用时。如果试剂供应商已经检查过适用性，则不需要重复这个测试。新的物质批准和新的滴定剂批号不需要重复该测试。
46. When should I apply Chapter 2.9.40 ‘UNIFORMITY OF DOSAGE UNITS’?
什么时候我应该使用第2.9.40章“剂量单位均匀度”？
From a pharmaceutical quality point of view, the approach taken in the harmonised general chapter on uniformity of dosage units (2.9.40) is considered equivalent to what was required in general chapters 2.9.5 and 2.9.6. Thus, the decision on what approach to take is left to the user. Either 2.9.40 or 2.9.5 and 2.9.6 may be applied to demonstrate compliance with the Ph. Eur. with regard to the uniformity of dosage units.
从药品质量的观点来说，在协调过的剂量单位均匀度通则（2.9.40）中所采用的方法被认为是等同于通则2.9.5和2.9.6的要求。因此，用户可以自行决定采用何种方法。通则2.9.40和2.9.5及2.9.6都可以用来证明符合EP的剂型均一性要求。
For more details, you can also consult the Questions & Answers provided by the Quality Working Party of the European Medicines Agency on their website
更多细节，你可以参见EMA质量工作组在其网页上公布的问答。
47. In Chapter 2.6.12 under section 4-4 ‘GROWTH PROMOTION OF THE MEDIA’, there is a statement that reads “For solid media, growth obtained must not differ by a factor greater than 2 from the calculated value for a standardised inoculum’’. Does the statement mean that the difference can be twice or half the calculatedvalue of inoculum?
在2.6.12章第4-4部分“培养基促生长试验”中，有一个声明说“对于固体培养基，所获得的生长情况与标准接种物计算值差异级别不得大于2”。该说明是讲差异可以是接种物计算值的两倍至一半吗？
Your interpretation is correct. If the inoculum is 100 CFU, then the recovery must be between 50 and 200 CFU.
你的理解是正确的。如果接种物是100CFU，则回收率必须在50-200CFU之间。
49. Should we use “sulf...” or “sulph...”（指硫化物） for our substance in
English?
我们物质写成英文时是应该用“sulf-”还是应该用“sulph-”？
At its June 2009 meeting, the European Pharmacopoeia Commission has decided to apply IUPAC and WHO INN rules. Therefore the spelling “Sulfate” instead of “sulphate” will be used in the 7th edition of the European Pharmacopoeia.
在2009年6月的会议上，EP委员会已经决定应用IUPAC和WHO INN命名规则。因此，在EP第7版里开始使用“sulfate”替代“sulphate”。
This change has been made for consistency purposes on
此变更仅是为了协调一致，不会对药用活性物质或辅料的质量水平要求产生影响。
There will be a transition period, where the spelling could differ from the official European Pharmacopoeia name.
期间会有一个过渡阶段，拼写可以与EP中的正式名称不同。
During this transition period name changes will occur:
在过渡阶段，当以下情形发生时将会变更名称：
? For Certificates of Suitability when new revisions or renewals are granted;
? CEP修订或更新重新颁发时
? For Reference Standards when new/replacement batches of are released.
? 对照品发行新批号或替换时