GB 22613-2008Cartap hydrochloride water soluble powders (English PDF)

3.1 Composition and appearance

This product should be compliant CARTAP original drug is made, the appearance of a homogeneous loose powder, without clumps.

3.2 CARTAP soluble powders should meet the requirements of Table 1.

Table 1 CARTAP soluble powders Control Project Index

project

index

50% 95%

CARTAP mass fraction /% 50.0 + 95.0 + 2.5-2.5 2.5-2.5 Moisture content /% <= 3.0 1.5 Score a /% Water insoluble mass <= 0.6 pH range 3.0 to 6.0 the degree of dissolution and solution stability (through 75µm sieve) a /% (5min after residue) <= (18h after residue) <= 1.0 0.05 Thermal storage stability test a qualified a normal production of water insoluble matter, the degree of dissolution and solution stability, thermal storage stability test every three months at least once.

Test Method 4

4.1 Sampling

According to GB/T 1605-2001 "on solid preparation sampling" approach. Determined by sampling a random number table method packages, the final sample size not less than 300g.

4.2 Identification Test

HPLC --- The identification test can be carried out simultaneously with the determination of the mass fraction of CARTAP. In the same chromatographic operating conditions , The sample solution to a chromatographic retention time and CARTAP CARTAP standard solution peak retention time should be relative difference 1.5% or less.

Determination of the mass fraction of 4.3 CARTAP

4.3.1 Method summary

Phosphoric acid aqueous sample was dissolved in heptane solution of sodium + acetonitrile as mobile phase, to use as filler Capcel-PakC18 stainless steel Column and UV detector (225nm), the sample of CARTAP reverse phase high performance liquid chromatography, external standard.

4.3.2 Reagents and solutions

Acetonitrile. HPLC grade;

Water. The new secondary steam distilled water;

Phosphoric acid;

Phosphoric acid. water with phosphoric acid adjusted to pH 2.5;

Geng sodium;

Triethylamine;

Heptane sulfonate solution. Weigh 3.64g of sodium heptanoate in 1L wide-mouth bottle, add distilled water 900mL secondary shaking to dissolve, Phosphoric acid was added 16mL; then triethylamine adjusted to pH 2.0;

CARTAP standard. a known mass fraction >=99.0%.

4.3.3 Instruments

High performance liquid chromatography. a variable wavelength UV detector;

Chromatographic data processor or chromatography workstation;

Column.200mm × 4.6mm (. I.d) stainless steel column, built Capcel-PakC18,5µm filler (or with equivalent effect color the column);

Filter. pore size of about 0.45µm;

Micro injector. 50µL;

Quantitative sample line. 10µL;

Ultrasonic cleaner.

4.3.4 HPLC operating conditions

Mobile phase. psi (heptane solution of sodium. acetonitrile) = 90.10, with 0.45µm filter membrane, ultrasound 10min spare;

Flow rate. 1.0mL/min;

Column temperature. room temperature (temperature change should not exceed 2 °C);

Detection wavelength. 225nm;

Injection volume. 10µL;

Retention time. 7.4min.

It said operating parameters are typical, according to the characteristics of different instruments, given operating parameters adjusted as appropriate, in order to obtain the best results.

Typical CARTAP soluble powders HPLC is shown in Figure 1.

1 --- CARTAP.

Figure 1 CARTAP soluble powders by high performance liquid chromatogram

4.3.5 Measuring step

4.3.5.1 Preparation of standard solution

Weigh 0.05g (accurate to 0.0002g) CARTAP standard, a 50mL volumetric flask, dissolved in aqueous phosphoric acid and diluted to the mark Degree, shake.

4.3.5.2 Preparation of sample solution

Weigh containing CARTAP 0.05g (accurate to 0.0002g) sample, placed in 50mL volumetric flask, and diluted with aqueous phosphoric acid to the mark.

4.3.5.3 Determination

Under these operating conditions, after the instrument is stable, continuous injection of several doses of the standard solution until the two adjacent needles fenitrothion Danfeng area relative change After less than 1.5%, according to the solution, sample solution, sample solution, standard order of standard solution was measured.

4.3.5.4 Calculation

The two needle sample solution and measured before and after the two doses of the standard sample solution fenitrothion Danfeng area were averaged. Sample CARTAP the mass fraction of 1 (%) according to equation (1).

Where.

A1 --- standard solution, fenitrothion mean Danfeng area;

A2 --- sample solution, fenitrothion mean Danfeng area;

--- CARTAP standard mass fraction, expressed as a percentage.

4.3.6 Allowable difference

CARTAP relative deviation of the mass fraction of two parallel determination results shall not be greater than 1.5%, the arithmetic mean value as a measurement result.

4.4 Determination of Moisture

According to GB/T 1600 in "azeotropic method".

4.5 Determination of insoluble matter

4.5.1 Reagents and Instruments

Conical flask. 250mL;

Glass sand core crucible. G3;

Oven. 105 °C ± 2 °C;

Suction flask. 500mL.

4.5.2 Determination

Weigh 10g sample (accurate to 0.01g), into a conical flask, 100mL water, shaking the sample has been dissolved immediately by Constant weight (accurate to 0.0002g) filter crucible, and then 60mL of water, washed three times Erlenmeyer flask filtration. The crucible was placed in an oven dried 2h, brought out in the dryer to cool and weigh (accurate to 0.0002g).

4.5.3 Calculation

Sample water insolubles 2 (%) according to equation (2).

Where.

4.5.4 Allowable difference

Relative deviation parallel determination results shall be not more than 30% of the arithmetic mean as a measurement result.

According to GB/T 1601 carried out.

4.7 Degree of dissolution and solution stability

4.7.1 Method summary

The sample was dissolved in dissolution degree is 25 °C standard hard water, invert 15 times, standing 5min, filtered through a 75µm test sieve, quantitative measurement Given the sieve residue. The solution stability is the solution to stand after 18h, again using the test sieve, sieve residue quantitatively determined.

4.7.2 Instruments

Standard sieve. aperture 75µm, diameter 76mm;

Stoppered cylinder. between 250mL (0mL ~ 250mL scale distance 20cm ~ 21.5cm, 250mL graduated from the line and the bottom plug from a 4cm ~ 6cm).

Standard hard water. 342mg/L, prepared according to GB/T 1603 in the appropriate method.

4.7.3 Preparation of sample solution

In the graduated cylinder was added 250mL 2/3 standard hard water, its temperature was adjusted to 25 °C, 5g of the sample, a standard hard water added to the mark.

Stoppered. Standing 30s, inverted measuring cylinder 15 times by hand, is reset. Reversed, once used by the reset time should not exceed 2s.

The sample solution was allowed to stand in the cylinder after 5min ± 30s, on into the constant weight 75µm sieve, and the filtrate was collected 500mL burn Cup, reserved for the next test. 20mL graduated cylinder with distilled water five times, all insolubles were quantitatively transferred to a sieve, discard the washing liquid, Check the sieve residue. If there is residue on the sieve, sieve 60 °C dried to constant weight, weighed in.

The filtrate was allowed to stand 18h, carefully observe whether the precipitation filtrate in the beaker. If there are insoluble materials, and then the sample was constant weight 75µm test sieve, sieve test with 20mL of distilled water 5 times, if there is the presence of crystalline solids or sieve, sieve dry at 60 °C Drying to constant weight and weighed.

4.7.6 Calculation

5min after the residue 3 (%) according to equation (3) Calculated.

Where.

18h after residue 4 (%) according to equation (4) Calculated.

Where.

4.8 Thermal storage stability test

According to GB/T 19136 "other agents" to. After the heat storage CARTAP content should not be less than the mass fraction of the reservoir before CARTAP 97%.

4.9 Product testing and acceptance

Shall comply with GB/T 1604 regulations limit the use of numerical processing rounding value comparison method.