主题：【求助】再问些西药制剂方面的内容，还有点气相参数．

原文由 mhq111111 发表:
This practice was necessary due to the large sample-to-sample variability that has been observed from samples pulled from different filing time points in the process （i.e.，differences are observed from vials pulled at the beginning，the middle and the end of the filling process）。
这句话的理解最好能帖一段上文，自己的理解是精确度随取样时间的不同有差异。比如用色谱法，指的是开始做试验时，试验中期，试验结束时。会不会是做几天内的稳定性实验呢？猜测。

刚有点事出去了一下．

Accuracy at the Degradation Product Level
The accuracy of the method for quantitation of the degradates of BK-55 was
determined by spiking BK-55 standard solution into placebo solution, as described for linearity determinations. Six concentrations between 0.05% and 9.4o/o% of the method conceniration were evaluated. The individual solutions for each level were prepared in duplicateion each of two days and were analyzed by the subject method.The mean recoveries for BK-55 Free Acid at the degradate level ranged from 97 .3oh to l00.9%. Thii method demonstrates acceptable accuracy at the degradation product level.

Precision
RepeatabilitY
Sample-to- Sample VariabiIity


Sample precision was evaluated by analysis of six separate preparations from one stock solution. This practice was necessary due to the large sample-to-sample variability that has been observed from samples pulled from different filing time points in the process (i.e., differences are observed from vials pulled at the beginning, the middle and the end of the filling process). The peak area counts for each preparation were then calculated for the sarnple precision. The RSD was 0.2% for BK-55 sodium and 0.5oh to10.5% for the degradaies and impurities. These data demonstrate acceptable method precision. The results are summarized in Table 4.

原文由 nanfeiyan9999 发表:

Accuracy at the Degradation Product Level
The accuracy of the method for quantitation of the degradates of BK-55 was
determined by spiking BK-55 standard solution into placebo solution, as described for linearity determinations. Six concentrations between 0.05% and 9.4o/o% of the method conceniration were evaluated. The individual solutions for each level were prepared in duplicateion each of two days and were analyzed by the subject method.The mean recoveries for BK-55 Free Acid at the degradate level ranged from 97 .3oh to l00.9%. Thii method demonstrates acceptable accuracy at the degradation product level.

鉴于本人水平，只能粗略告诉你这两段文字分别描述的中心内容是：（第一段）加标回收率（准确度）和（第二段）精密度（重现性，n=6）

Precision 精密度
RepeatabilitY 重现性
Sample-to- Sample VariabiIity 针与针之间的差异


Sample precision was evaluated by analysis of six separate preparations from one stock solution. This practice was necessary due to the large sample-to-sample variability that has been observed from samples pulled from different filing time points in the process (i.e., differences are observed from vials pulled at the beginning, the middle and the end of the filling process). The peak area counts for each preparation were then calculated for the sarnple precision. The RSD was 0.2% for BK-55 sodium and 0.5oh to10.5% for the degradaies and impurities. These data demonstrate acceptable method precision. The results are summarized in Table 4.

filling process我的理解是6个进样小瓶放同一种液体，测试重现性。由于进样时间不同，结果会有误差。事实上，短期的稳定性实验也是这样做，不过时间间隔为0，4，8，12，24，48h。

鉴于本人水平，只能粗略告诉你这两段文字分别描述的中心内容是：（第一段）加标回收率（准确度）和（第二段）精密度（重现性，n=6）
哈哈这部分和我的理解一样的．

Precision 精密度
RepeatabilitY 重现性
Sample-to- Sample VariabiIity 针与针之间的差异



filling process我的理解是6个进样小瓶放同一种液体，测试重现性。由于进样时间不同，结果会有误差。事实上，短期的稳定性实验也是这样做，不过时间间隔为0，4，8，12，24，48h。

My job is not related to medicine nor chemistry, therefore, 只能在外围转转, 挑挑刺

Quoted:
（第一段）加标回收率（准确度）和（第二段）精密度（重现性，n=6）
Precision 精密度
RepeatabilitY 重现性
Sample-to- Sample VariabiIity 针与针之间的差异

Response:
When I read the Chinese books, I was sometimes confused by the terms重复性, 再现性, 重现性, 复现性……  I therefore suggest that we should use the terms stipulated in the national standards as far as possible.
Referring to JJF1001-1998 通用计量术语及定义, Repeatability is 重复性 (Clause 5.6) and Reproducibility is 复现性 (Clause 5.7)

The terms in this national standard may not be the best (in fact, I prefer 再现性 for Reproducibility so as to avoid the word 复 appears in both Repeatability and Reproducibility), but using the consistent technical terms national wide can minimize the misunderstanding.

[Remark : Accuracy and Precision are qualitative words, described with good, high, moderate, sufficient etc.  Repeatability and Reproducibility are quantitative words, expressed with values (standard deviation, range etc.), but not the number of sample, I think that the “n=6” is a short form for “statistical analysis from 6 samples”]

=====================================================================

Quoted:
Sample precision was evaluated by analysis of six separate preparations from one stock solution.

Response:
This may be a sampling issue.
Samples should represent the population.  For this case, all “six separate preparations (i.e. samples)” must be taken “from one stock solution”.
Why doing this (i.e. “why from one stock solution”) ?  The subsequent sentence “This practice was necessary due to the large sample-to-sample variability ………” explains the reason .

1．Annotated pages from Part1 Specificaitons and clean pages of Section 1 Specifications are attached。
说明书PartⅡE 1.1部分注释页和说明书Section 3.2.P.5.1相互联系。（“相互联系”是否有更好的翻译方法？）

-----→＞﹥同意2楼：一般说来……are attached是见附件的意思。比如参考EP制定了一个质量标准，就要把EP作为附件列在资料后面，这时就用attatched。再比如电子邮件的附件也可以用attatched.


2．Scale Up Batch#3
工艺放大后的批号3样品（注释：表格的一个空格内容）

-----→＞﹥工艺放大后的第3个批号

3．Engineering Run（注释：是否有人在类似翻译里见过这个？）

-----→＞﹥同意3楼：engineering run－这个词在工程学里有试生产、工程验证的意思。通常在正式生产前进行。

4．This practice was necessary due to the large sample-to-sample variability that has been observed from samples pulled from different filing time points in the process （i.e.，differences are observed from vials pulled at the beginning，the middle and the end of the filling process）。因为在不同时间装瓶的样品可观察到明显的样品间差（如：在样品测定发现，装瓶的前期，中期和后期装入药瓶的样品，测定结果即具有差异）。（注释：前期中期后期是什么啊？）
mhq111111: 请指出这个实验测定的是什么项目？我直觉不是装瓶而是从瓶中抽取液体。

不同意23楼：filling process我的理解是6个进样小瓶放同一种液体，测试重现性。由于进样时间不同，结果会有误差。事实上，短期的稳定性实验也是这样做，不过时间间隔为0，4，8，12，24，48h。

-----→＞﹥filling process我的理解：虽然vial可以指HPLC 或 GC进样时用的进样瓶也可以指放进注射液的药品瓶，我认为samples pulled from different filing time points in the process 是指在灌装注射液（或药粉）入药品瓶的生产过程中，从不同灌装时间点拿出的样品瓶。at the beginning，the middle and the end of the filling process是指在一个生产批号中在生产的开始、中间和结束时的时间段（或点）。总体大意是：英文作者想说精确度(重现性，n=6, 在同一实验室内用同样一个样品储液)随生产中取样的不同有大的差异（虽然我认为不好理解）

-----→＞﹥i.e.是Latin字id est的缩写， 中文意思：that is(也就是)



5．The changes in chromatographic performance for BM-55 may result from the degredates pH dependent ionization state。
BM-55色谱参数改变可能来自于降解产物pH依赖的离子状态。

-----→＞﹥同意11楼：降解产物的离子状态取决于pH，这就是BM-55色谱行为改变的原因。  May: 就是


6．色谱柱: Poraplor Q-HT (25 m x0.53 mm, with a 2.5 m particle trap), 20 μm film thickness or equivalent column

。
进样器: 200℃, packed inlet w/adapter
Helium Flow（carrier gas）: 8mL/ min. 氦气流速 (载气)
Reference Flow: 48 ml/min.
Auxilliary Flow: 4 nil/mrn. （注释：气相的参数相，都是什么意思啊？我查了以前HPPY斑竹发过的一个相关帖子和其他资料，但还是不明白。辅助气应该是空气和氢气，但Reference Flow: 48 ml/min.是空气吗？）


-----→＞﹥我不知道，同意16楼


7．Determination of Net Contents Assay，Degradates，Content Uniformity and Identity of EP-55 in the Drug Product by Gradient HPLC。通过HPLC梯度洗脱法检测药品中EP-55效价,降解产物,含量均匀度和鉴定厄他培南.（注释：本文为抗生素，其中Assay应该翻译成效价，但整句总觉得协调不好。）通过HPLC梯度洗脱法来做该药品的鉴别、含量均匀度和主成分与降解产物的定量。

-----→＞﹥Net Contents Assay 应该翻译成：活性物净含量（主成分或有效组分含量）


8．Weigh approximately 50mg of a previously released lot of EP-55 drug substance into a 25mL volumetric flask。称量约50mg以前生产的BM-55药品，放入25ml容量瓶中。（注释：apreviously released lot怎么翻译合适？）

-----→＞﹥同意11楼： 在本批样品之前放行的批次（既然是放行，肯定是检验合格的，lqqer的理解是对的）。质量保证部门（QA，在北美药厂内部唯一有权放行药品批号的部门）已经放行了的批号，可能在仓库或已经销售到市场。


9．Those peaks which are bulk drug process impurities are disregarded，since they are controlled in the active pharmaceutical ingredient。不考虑原料药杂质峰，因为其在活性成分中的含量得到控制。（注释：整句因果关系及bulk drug process impurities是什么？）

-----→＞﹥同意11楼：因为在活性成分中已经控制了原料药杂质，因此原料药杂质峰可忽略。bulk drug是那种大桶装的药物（一般是先用双层塑料袋包好再放入桶中），既可以是原料药，也可以是制剂中间体或还没有进行市售包装的成品。process impuroties是工艺杂质，是指药品在制备工艺过程中引入的杂质，它包括原料药中本身含有的杂质、没有反应完全的反应物、反应过程中所生成的中间体及副产物、反应过程中所使用的试剂及催化剂等。工艺杂质和降解产物是药品中最主要的杂质。


10．Inject the Sample Preparations such that each sample set is bracketed by a Working Standard Solution。注入样品，每个样品组由进样用标准溶液得到。

-----→＞﹥同意11楼：每个样品组进样前先进一针工作标准品溶液。
          对于HPLC进样：如果测定活性成分含量，一般进样顺序是：Trial STD Solution (Check system suitabilty to meet USP 30 supp. 1 & 2 requirments, such as Retention Time, resolution, USP Plate Count, k prime = capacity factor and/or tailing factor ) →　5 or 6 STD Injections (Meet RSD requirments) → Control STD Injection (Meet recovery requirments) → 5 or 6 Sample (SPL) Injections → Check STD Injection→ 5 or 6 Sample (SPL) Injections → Check STD Injection →....

原文由 nanfeiyan9999 发表:
Precision 精密度
RepeatabilitY 重现性
Sample-to- Sample VariabiIity 针与针之间的差异

repeatablity是重复性，是指同一实验室的分析人员用相同的分析法在短时间内对同一样品重复测定结果之间的相对标准偏差。reproducibility才是重现性（又叫再现性），是指不同实验室的不同分析人员用相同分析对同一被测对象测定结果之间的相对标准偏差。）

原文由 penn007 发表:
filling process我的理解：虽然vial可以指HPLC 或 GC进样时用的进样瓶也可以指放进注射液的药品瓶，我认为samples pulled from different filing time points in the process 是指在灌装注射液（或药粉）入药品瓶的生产过程中，从不同灌装时间点拿出的样品瓶。at the beginning，the middle and the end of the filling process是指在一个生产批号中在生产的开始、中间和结束时的时间段（或点）。

同意这个观点。

原文由 happyjyl 发表:

repeatablity是重复性，是指同一实验室的分析人员用相同的分析法在短时间内对同一样品重复测定结果之间的相对标准偏差。reproducibility才是重现性（又叫再现性），是指不同实验室的不同分析人员用相同分析对同一被测对象测定结果之间的相对标准偏差。）

Basically correct, but not completely.
For the full details of Repeatability and Reproducibility, please refer to Clause 5.6 and 5.7 of JJF1001-1998 通用计量术语及定义

When I was deployed to the laboratory several years ago, I knew very little about testing.  I even did not know whether error = indicated value – true value or true value – indicated value.  At that time, the “International Vocabulary of Basic and General Terms in Metrology (VIM)” was my ABC book for my career in metrology.

The VIM and JJF1101-1998 are highly recommended for everyone in the field of testing.

JJF1001-1998 籵蚚數講扲逄摯隅砱
JJF1001-1998 通用计量术语及定义