(1) Brief description

The minimum filling quantity inspection method (2015 edition of "Chinese Pharmacopoeia" General Rules 0942) is applicable to solid, semi-solid and liquid preparations

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Except for the preparations and radiopharmaceuticals with differences in weight (packing) specified in the General Rules of Preparations, the inspection shall be carried out in the following manner

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(2) Operation method

1.

The gravimetric method is applicable to those whose declared quantity is by weight

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Unless otherwise specified, take 5 test samples (3 samples with a marked capacity of 50g or more), remove the outer cover and label, clean and dry the outer wall of the container with a suitable method, accurately weigh them, and remove the contents.

The container is washed with a suitable solvent and dried, and then the weight of the empty container is accurately weighed, and the content and average content of each container are calculated

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2.

The volumetric method is applicable to those whose marked capacity is calculated by volume

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Unless otherwise specified, take 5 test samples (3 samples with a marked capacity of 50ml or more).

When opening, take care to avoid loss and transfer the contents to a pre-standardized dry measuring cylinder (the size of the measuring tool).

The volume to be measured should be at least 40% of its rated volume).

After the viscous liquid is poured out, unless otherwise specified, invert the container for 15 minutes and try to empty it out

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Use a pre-standardized dry volumetric syringe to drain the volume of 2ml or less

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Read the volume of the contents of each container and find the average volume

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(3) Matters needing attention

1.

Care should be taken to avoid loss when opening the cap

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2.

In the two weighings of each test product, attention should be paid to the sequence of numbers and the matching of empty containers (weight method)

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3.

Do not touch the test product directly with your fingers during the weighing process (weight method)

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4.

The graduated cylinder used should be clean, dry, and calibrated regularly; its maximum capacity should be consistent with the labelled volume of the test product, or no more than 2 times the labelled volume (volume method)

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5.

After the contents of the test product are poured into the graduated cylinder, the container should be inverted for 15 minutes to make it as full as possible, and then read the content of each container (volume method)

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(4) Results and judgment

1.

The content of each container is not less than the minimum allowable volume, and the average volume is not less than the marked volume, it is judged to meet the requirements (Table 15-26)

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Table 15-26 Limits of minimum filling quantity inspection

Note: The average filling volume and the filling volume of each container are calculated as a percentage based on the marked filling volume, and three significant figures are used to judge the result

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2.

If the volume of one container does not meet the requirements, another 5 (3 retests for 50g or more than 50ml) are retested and the results all meet the requirements, and it can still be judged to meet the requirements

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3.

The average filling volume of the initial test result is less than the marked filling volume, or the filling volume of more than one container does not meet the requirements, or the retest still fails to meet the requirements; all are judged to be non-compliant

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(5) Records and calculations

1.

Record the room temperature, the labelled volume, specifications, the reading (ml) of the contents of each container, or the weight of each test product and the weight of the empty container, and calculate the volume of each container

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2.

Divide the total volume of each container by 5 (or 3) to get the average volume

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3.

Find the volume and average volume of the contents of each container, and calculate the minimum allowable volume

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2.

Ethanol content determination method (General Principle 0711)

(1) Gas chromatography

1.

Brief introduction This method uses gas chromatography to determine the ethanol content (%) (v/v) in various preparations at 20°C

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Unless otherwise specified, it shall be determined according to the following methods

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2.

Method of operation

(1) The first method (capillary column method)

1) Chromatographic conditions and system suitability test: a capillary column with (6%) cyanopropyl phenyl-(94%) dimethyl polysiloxane as the fixed liquid; the starting temperature is 40°C and maintained for 2 minutes, The temperature is increased to 65°C at a rate of 3°C per minute, and then to 200°C at a rate of 25°C per minute, and maintained for 10 minutes; the temperature of the inlet is 200°C; the temperature of the detector (FID) is 220°C; split injection, split flow The ratio is 1:1; the headspace sampling equilibrium temperature is 85°C, and the equilibrium time is 20 minutes

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The number of theoretical plates calculated based on the ethanol peak should not be less than 10,000, and the separation between the ethanol peak and the n-propanol peak should be greater than 2.

0

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2) Calibration factor determination: accurately measure 5ml of absolute ethanol at a constant temperature of 20°C±1°C , and average two copies; place in a 100ml measuring flask, and precisely add n-propanol (internal standard substance) at a constant temperature of 20°C±1°C 5ml, dilute with water to the mark, shake well, accurately measure 1ml of the above solution, put it in a 100ml measuring flask, dilute to the mark with water, shake well (if necessary, further dilute), as the reference solution

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Accurately measure 3ml, place it in a 10ml headspace sample bottle, seal it, inject the sample in the headspace, inject each reference solution 3 times, measure the peak area, calculate the average correction factor, and the relative standard deviation of the obtained correction factor shall not be greater than 2.

0 %

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3) Determination method: Precisely measure an appropriate amount of the test product (equivalent to about 5ml of ethanol) at a constant temperature of 20℃±1℃, put it in a 100ml measuring flask, and precisely add 5ml of n-propanol at a constant temperature of 20℃±1℃ with water Dilute to the mark, shake well, accurately measure 1ml of the above solution, place it in a 100ml measuring flask, dilute to the mark with water, shake well (if necessary, further dilute), as the test solution

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Accurately measure 3ml, place it in a 10ml headspace sampling bottle, seal, headspace sampling, measure the peak area, calculate, and get it

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(2) The second method (packed column method)

1) Chromatographic conditions and system suitability test: use divinylbenzene-ethylvinylbenzene type polymer porous beads with a diameter of 0.

18～0.

25mm as the carrier, and the column temperature is 120～150℃

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The number of theoretical plates calculated based on the n-propanol peak should not be less than 700, and the resolution between the ethanol peak and the n-propanol peak should be greater than 2.

0

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2) Calibration factor determination: accurately measure 4ml, 5ml, 6ml of absolute ethanol at a constant temperature of 20℃, put them into a 100ml measuring flask, respectively, precisely add 5ml of n-propanol (internal standard substance) at a constant temperature of 20℃, and dilute with water To the mark, shake up (if necessary, further dilute), as a reference solution

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Take appropriate amounts of each of the above three solutions and inject them into the gas chromatograph, respectively, inject three consecutive samples, measure the peak area, and calculate 9 correction factors.

The relative standard deviation of the obtained correction factors shall not be greater than 2.

0%

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3) Determination method: Precisely measure an appropriate amount of the test solution at a constant temperature of 20°C (equivalent to about 5ml of ethanol), place it in a 100ml measuring flask, and accurately add 5ml of n-propanol at a constant temperature of 20°C, dilute to the mark with water, and shake Evenly (if necessary, further dilution), as the test solution

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Take an appropriate amount and inject it into the gas chromatograph, determine it, and get it

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3.

Matters needing attention

(1) In the chromatogram of the test solution containing no internal standard substance, no impurity peak should appear at the position corresponding to the peak of the internal standard substance

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(2) When using a capillary column for measurement, if it does not meet the requirements of the system suitability test, the column temperature can be appropriately increased for aging before the measurement

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(3) When using other carriers, the system suitability test must comply with the provisions of this law

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4.

Results and Judgment

(1) The standard deviation of the measurement data of the two test solution should not be greater than 1.

5%, otherwise the measurement should be repeated

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(2) If the amount of ethanol in the test solution is within the limit specified in the standard, it is judged to meet the requirements

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5.

Records and calculations

(1) recording instrument model and the detector, column, column temperature, using the reagents and the like

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(2) Record the sampling volume, dilution factor, correction factor and peak area of the reference substance and the test substance

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(3) Calculate the measurement result of the amount of ethanol

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In the formula, As is the peak area of the internal standard substance; AR is the peak area of the reference substance; Cs is the concentration of the internal standard substance solution; CR is the concentration of the reference substance solution

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In the formula, Ax is the peak area of the test substance; Cx is the concentration of the test solution; As is the peak area of the internal standard substance; Cs is the concentration of the internal standard substance; f is the correction factor

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