GB 24754-2009Prometryn technical (English PDF)

4.1 Sampling

According to GB/T 1605-2001 "on the original drug product sampling method". Determining sample package using a random number table method; the final sample the amount of not less than 100g.

4.2 Identification Test

Gas Chromatography --- The identification test can be carried out simultaneously with the determination of the mass fraction of Prometryne. Under the same chromatographic operating conditions, the test Retention time with the standard solution of a sample solution peaks in Prometryne chromatographic retention time, the relative difference should be less than 1.5%.

Infrared spectroscopy --- sample and standard samples Prometryne in 4000cm-1 ~ 400cm-1 wave number range of the infrared spectrum should not significantly Differences. Prometryne Sample standard infrared spectrum shown in Figure 1.

Figure 1 Prometryne standard infrared spectrum

4.3 Determination of the mass fraction of Prometryne

4.3.1 Method summary

Sample was dissolved in chloroform to triadimefon as internal standard, the use of the inner wall of the bonded Carbowax 20M capillary column and flame Ionization detector to sample Prometryne gas chromatographic separation and determination. You can also use packed column gas chromatography, chromatographic conditions Senate See Appendix A.

4.3.2 Reagents and solutions

Chloroform;

Triadimefon. should not interfere with the analysis of impurities, >=95%;

Prometryne Sample. Known Prometryne mass fraction, >=99.0%;

Internal standard solution. Weigh 8.6g triadimefon, placed 1000mL volumetric flask with chloroform to dissolve and dilute to volume, shake.

4.3.3 Instruments

Gas chromatograph. with a hydrogen flame ionization detector;

Chromatographic data processor or chromatography workstation;

Column. 30m × 0.32mm (. I.d) capillary column, the inner wall of the bonding polyethylene glycol 20M, film thickness 0.25 m;

Micro injector. 10µL.

4.3.4 GC operating conditions

Temperature (°C). 195 Column temperature gasification chamber 230, detection chamber 230;

Gas flow rate (mL/min). carrier gas (N2) 2.0, hydrogen gas 30, air 300;

Injection volume (µL). 1.0;

Retention time (min). Prometryne about 4.2, internal standard (triadimefon) about 5.6.

GC operating conditions described above, the Department of typical operating parameters. According to the characteristics of different instruments, given operating parameters adjusted as appropriate, in order to obtain the best results. Typical Prometryne original drug and the internal standard gas chromatography is shown in Figure 2.

1 --- Prometryne;

2 --- internal standard (triadimefon).

Figure 2 Prometryne gas chromatogram of the drug and the internal standard

4.3.5 Measuring step

4.3.5.1 Preparation of standard solution

Weigh Prometryne standard 0.1g (accurate to 0.0002g), placed in 15mL stoppered glass bottle with a pipette moved 10mL internal standard Solution, shake.

4.3.5.2 Preparation of the sample solution

It weighs about 0.1g sample containing Prometryne of (accurate to 0.0002g), placed in 15mL stoppered glass bottle, in use with 4.3.5.1 with a pipetted into internal standard solution 10mL, shake.

4.3.5.3 Determination

Under these operating conditions, the instrument until a stable baseline, the number of continuous injection doses of the standard solution, calculated for each needle Prometryne and the internal standard peak area Repeatability ratio, when two needles Prometryne relative change compared with the internal standard peak area of less than 1.2%, according to the standard solution, sample to be adjacent Solution, sample solution, the order of the standard solution was measured.

4.3.6 Calculation

The two needle sample solution and measured before and after the two doses of the standard sample solution Prometryne and the internal standard peak area ratio in the average respectively.

Prometryne sample mass fraction of 1 (%), according to equation (1).

Where.

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

4.3.7 Allowable difference

The difference between two parallel determination results shall not be greater than 1.5%, the arithmetic mean value as a measurement result.

4.4 Determination of loss on drying

4.4.1 Instruments

Weighing bottle. diameter 50mm, height 30mm.

Oven. 90 °C ± 2 °C.

Dryer.

4.4.2 Measuring step

The weighing bottle placed in an oven bake 1h, cooled to room temperature and placed out, weighed (accurate to 0.0002g) in a desiccator. Repeat the above Step, until constant weight weighing bottle. Take 5.0g sample was already drying to constant weight weighing bottle, paving, weighed (accurate to 0.0002g), the weighing bottle and cap separately placed in an oven, and bake for 1h, cover, take out into the dryer to cool to room temperature and weigh (to the nearest 0.0002g).

4.4.3 Calculation

2 Loss on drying (%) according to equation (2).

Where.

4.5 Determination of the mass fraction of sodium chloride

4.5.1 Reagents and solutions

acetone;

Sulfuric acid solution. (H2SO4) = 50%;

Hydrochloric acid standard solution. Ba (HCl) = 0.1mol/L, according to GB/T 601 preparation and calibration;

Standard silver nitrate titration solution. Ba (AgNO3) = 0.1mol/L, according to GB/T 601 Preparation and calibration.

4.5.2 Instruments

Titrator;

Electrode. silver -217 type calomel electrode with salt bridge of potassium chloride.

4.5.3 Analysis of step

Weigh 5.0g sample (accurate to 0.0002g), in the 400mL beaker, 50mL acetone and dissolved by adding 200mL of water, with sulfur Acid solution of the sample solution is acidified to a pH of 1 to 2, with the pipette plus 2mL standard solution of hydrochloric acid, performed using standard silver nitrate titration solution Potentiometric titration.

4.5.4 Calculation

The mass fraction of sodium chloride in the sample 3 (%), according to equation (3) Calculated.

(Vp 1 Vp 2 Ba Ba 1- 2) (3) where.

The actual concentration of Ba 1 --- standard silver nitrate titration solution, expressed in moles per liter (mol/L);

Ba 2 --- the actual concentration of hydrochloric acid standard solution, unit mole per liter (mol/L);

Vp 1 --- titration, the volume of consumption of standard solution of silver nitrate, in milliliters (mL);

Vp 2 --- volume of the sample solution is added to the standard solution of hydrochloric acid, in milliliters (mL);

--- The M NaCl numerical molar mass in grams per mole (g/mol), [M = 58.5g/mol].

4.6 Determination of dimethylformamide two insolubles

According to GB/T 19138 performed. Using dimethylformamide solvent.

4.7 Product testing and acceptance

Shall comply with GB/T 1604's. Treatment of extreme values using the rounding value comparison method.