欧盟杂质计算标准的理解

menghlt

前辈们好，最近在研究EP9.4中对乙酰氨基酚检测方法，在杂质计算时出现了点问题，想请前辈指点迷津，单杂标准是不得过0.05%，是不超过对照液面积的0.05%还是不超过样品本身的0.05%呢？还有就是报告可忽略限度时忽略杂质未0.03%以下的杂质，还是忽略小于对照a溶液峰面积的0.03%呢？如果我丹灶算出来均小于0.03%，那么总杂报告为0吗？有点乱了，谢谢指导。EP9.4内容如下：Reference solution (c). Dissolve 5.0mg of paracetamol  purity J CRS in the solventmixture and dilute to 250.0 mLwith the solvent mixture. Dilute 1.0 mL of the solution to 200.0 mL with the solvent mixture.
Precolumn:
– size: l = 0.005 m, ? = 2.1 mm;
– stationary phase: end-capped solid core octadecylsilyl silica gel for chromatography R (2.7 μm)
Column:
– size: l = 0.10 m, ? = 2.1mm;
– stationary phase: end-capped solid core octadecylsilyl silica gel for chromatography R (2.7 μm)
– temperature: 30 ?C.
Mobile phase:
– mobile phase A: dissolve 1.7 g of potassium dihydrogen
phosphate R and 1.8 g of dipotassium hydrogen phosphate R
in water for chromatography R and dilute to 1000 mL with
the same solvent;
– mobile phase B: methanol R;

Flow rate: 0.3 mL/min.
Detection: spectrophotometer at 254 nm.
Injection: 5 μL
Identification of impurities: use the chromatogram obtained
with reference solution (b) to identify the peak due to
impurity K; use the chromatogram obtained with reference
solution (c) to identify the peak due to impurity J.
Relative retention with reference to paracetamol (retention
time = about 4min): impurity K = about 0.4 ; impurity J = about
10.1.
System suitability: reference solution (b):
– resolution: minimum 5.0 between the peaks due to
impurity K and paracetamol.
Calculation of percentage contents:
– for impurity J, use the concentration of impurity J in
reference solution (c);
– for impurity K, use the concentration of impurity K in
reference solution (b);
– for impurities other than J and K, use the concentration of
paracetamol in reference solution (a).
Limits:
– impurity K: maximum 50 ppm;
– impurity J: maximum 10 ppm;
– unspecified impurities: for each impurity, maximum
0.05 per cent;
Related substances. Liquid chromatography (2.2.29).
– total: maximum 0.2 per cent;
Solvent mixture: methanol R, water R (15:85 V/V).
– reporting threshold: 0.03 per cent, except for impurities J
Test solution. Dissolve 50.0 mg of the substance to be
and K.
examined in the solvent mixture and dilute to 5.0 mL with the
solvent mixture.
Reference solution (a). Dilute 1.0 mL of the test solution to
100.0 mL with the solvent mixture. Dilute 1.0 mL of this
solution to 20.0 mL with the solvent mixture.
Reference solution (b). Prepare immediately before use.
Dissolve 5.0 mg of paracetamol impurity K CRS and 5 mg of
paracetamol CRS in the solvent mixture and dilute to 100.0 mL
with the solvent mixture. Dilute 1.0 mL of the solution to
100.0 mL with the solvent mixture.

希望370283

For impurities other than J and K, use the concentration of paracetamol in reference solution (a); Reference solution (a). Dilute 1.0 mL of the test solution to 100.0 ml with the solvent mixture. Dilute 1.0 mL of this solution to 20.0 mL with the solvent mixture.

1 mL/100 mL *1 mL/ 20 mL *100% = 0.05%

For impurities other than J and K: content = A(impurity)/Aa * 0.05%

wsx

杂质K J外标法计算，其他杂质自身对照法计算。

menghlt

希望370283 发表于 2018-3-23 08:47
For impurities other than J and K, use the concentration of paracetamol in reference solution (a);  ...

感谢，豁然开朗