GB 24755-2009Thiophanate-methyl technical (English PDF)

3.1 Appearance

White to gray powder.

3.2 Technical Specifications

Thiophanate-methyl original drugs should also meet the requirements of Table 1.

Table 1 thiophanate-methyl original drug control programs Index

Item Index

Thiophanate-methyl mass fraction /% >= 95.0 HAP (2- amino-3-hydroxy-phenazine) A mass fraction/(mg/kg) <= 0.5 DAP (2,3- diamino phenazine) A mass fraction/(mg/kg) <= 5.0 the pH range of 5.0 to 8.0 Loss on drying /% <= 0.5 when a normal production, HAP content, DAP mass fraction was measured at least once every three months.

Test Method 4

4.1 Sampling

Carried out in GB/T 1605-2001 of "original drug product sampling" approach. Determined by sampling a random number table method packages, the amount of the final sample not less than 100g.

4.2 Identification Test

HPLC --- This identification test can be carried out simultaneous determination of the content of thiophanate methyl and spirit. In the same chromatographic operating conditions , The peak of a retention time in the sample solution and the standard solution thiophanate-methyl retention time, the relative difference of 1.5% should be or less.

Infrared spectroscopy --- sample and thiophanate-methyl standard IR in the range 4000cm-1 ~ 400cm-1 absorption spectrum should ignorance Significant differences. Thiophanate-methyl standard infrared spectra of Figure 1.

FIG 1 thiophanate-methyl standard IR spectrum

4.3 Determination of the mass fraction of thiophanate-methyl

4.3.1 Method summary

Sample was dissolved in methanol, + water as the mobile phase, used Hypersil-ODS filler stainless steel column and UV detector (269 nm), thiophanate-methyl of the sample were separated by HPLC, external standard.

4.3.2 Reagents and solutions

Methanol. HPLC grade;

Water. The new secondary steam distilled water;

Thiophanate-methyl Sample. thiophanate-methyl known mass fraction, >=98.0%.

4.3.3 Instruments

HPLC. a variable wavelength UV detector;

Chromatographic data processor;

Column.200mm × 4.6mm (. I.d) stainless steel column, built-Hypersil-ODS, 5µm packing;

Filter. membrane pore size of about 0.45 m;

Microsyringe. 50µL;

Quantitative sampling tube. 10µL;

Ultrasonic cleaning.

4.3.4 HPLC operating conditions

Mobile phase. [Psi] (methanol. water) = 60.40, by membrane filtration, and degassing;

Flow rate. 1.0mL/min;

Column temperature. room temperature;

Detection wavelength. 269nm;

Injection volume. 10µL;

Retention time. thiophanate-methyl about 4.8min.

Are typical operating parameters of the above, according to the characteristics of different instruments, for a given operating parameters appropriately adjusted to obtain the best result.

Typical thiophanate-methyl original drug by HPLC is shown in Figure 2.

1 --- thiophanate-methyl.

Figure 2 HPLC thiophanate-methyl original drug

4.3.5 Determination Step

4.3.5.1 Preparation of standard solution

Thiophanate-methyl Weigh 0.1 g of standard sample (accurate to 0.0002g), a 50mL volumetric flask, dissolve and dilute to volume with methanol, Shake well. 5mL pipetted with the above solution diluted further with methanol 50mL volumetric flask to the mark.

4.3.5.2 Preparation of sample solution

Thiophanate-methyl, said sample is taken containing 0.1g (accurate to 0.0002g), a 50mL volumetric flask, dissolved in methanol and diluted to Mark and shake. A pipetted sample solution was diluted to 5mL above another in methanol 50mL volumetric flask to the mark.

4.3.5.3 Determination

Under the above operating conditions, after the instrument is stable, the number of consecutive doses of the standard solution is injected, the needle until two adjacent thiophanate methyl pk area opposite After the change is less than 1.2%, measured according to the standard solution, sample solution, the sample solution, the order of standard solution.

4.3.6 Computing

The measured sample solution and the preceding two needles two doses of the standard sample solution thiophanate-methyl pk area were averaged. A sample Mass fraction of 1-yl thiophanate (%), according to equation (1).

1 = A2

Where.

A1 --- the standard solution, the average area of thiophanate-methyl pk;

A2 --- sample solution, thiophanate-methyl pk average area;

--- Sample mass fraction thiophanate methyl, expressed in%.

4.3.7 Allows poor

Results difference between the two replicates thiophanate-methyl content should not exceed 1.2%, and the arithmetic mean value as a measurement result.

Determination of DAP and 4.4 HAP mass fraction

4.4.1 Method summary

Sample dissolved in mobile phase to a potassium dihydrogen phosphate buffer solution pH8.0 + methanol + water as mobile phase, used HypersilODS Stainless steel column filler and UV - VIS detector (453nm), and sample the HAP DAP reverse phase high performance liquid chromatographic from, external standard. (HAP, DAP detection limit of 2 × 10-9g, equivalent to 0.2mg/kg).

4.4.2 Reagents and solutions

Methanol. HPLC grade;

Potassium dihydrogen phosphate;

Water. The new secondary steam distilled water;

Sodium hydroxide solution. rho (NaOH) = 40g/L;

Buffer solution. Weigh 6.8g of potassium dihydrogen phosphate in distilled water with the secondary reagent bottle 1000mL, ultrasonic oscillation completely dissolved Solution, with a sodium hydroxide solution to pH 8.0;

Sample HAP. known HAP content, >=97.0%;

Sample DAP. DAP known mass fraction, >=99.0%.

4.4.3 Instruments

HPLC. a variable wavelength UV detector;

Chromatographic data processor;

Column.200mm × 4.6mm (. I.d) stainless steel column, built-Hypersil-ODS, 5µm packing;

Filter. membrane pore size of about 0.45 m;

Microsyringe. 250µL;

Quantitative sampling tube. 50µL;

Ultrasonic cleaning;

Centrifuge.

4.4.4 HPLC operating conditions

Mobile phase. [Psi] (methanol. water. buffer solution) = 45.25.30;

Flow rate. 1.0mL/min;

Column temperature. room temperature (temperature change should be less than 2 deg.] C);

Detection wavelength. 453nm;

Injection volume. 50µL;

Retention time. HAP about 3.6min; DAP about 10.6min.

Are typical operating parameters of the above, according to the characteristics of different instruments, for a given operating parameters appropriately adjusted to obtain the best result.

Of HAP, DAP standard sample by HPLC is shown in Figure 3, thiophanate-methyl original drug of HAP assay, HPLC DAP in Figure 4. FIG.

1 --- HAP;

2 --- DAP.

FIG 3 HAP and DAP standard liquid chromatography FIG.

1 --- HAP;

2 --- DAP.

HPLC FIG. 4 thiophanate-methyl original drug as measured in HAP and DAP

4.4.5 Determination Step

4.4.5.1 Preparation of standard solution

4.4.5.1.1 HAP Preparation of standard solution (A solution)

Sample HAP accurately weighed 0.025 g (accurate to 0.0002g) in brown 50mL volumetric flask, diluted with methanol to the mark, the super Was dissolved under sonication 10min, shake well and let to room temperature and set aside. (The solution was stable in the dark at 4 °C for 2 months.)

4.4.5.1.2 DAP Preparation of standard solution (B solution)

Sample DAP accurately weighed 0.025 g (accurate to 0.0002g) in brown 50mL volumetric flask, diluted with methanol to the mark, the super Was dissolved under sonication 10min, shake well and let to room temperature and set aside. (The solution was stable in the dark at 4 °C for 2 months.) Preparation 4.4.5.1.3 DAP, HAP standard solution Pipette 50µLA solution, 50µLB solution, diluted with a 25mL volumetric flask with brown flowing to the mark. (The standard the solution must be prepared before use. )

4.4.5.2 Preparation of sample solution

10.0 g was weighed accurately (accurate to 0.0002g) sample was brown 100mL volumetric flask, added with a pipette flow 50mL compatibility Was shaken under ultrasound 20min, shake well and let to room temperature. Then at 3000r/min centrifugal 5min, the supernatant was filtered.

4.4.5.3 Determination

Under the above operating conditions, after the instrument is stable, the number of continuous injection needle the DAP, HAP standard solution until two adjacent needles HAP, the DAP After the peak area relative variations are less than 20%, measured according to the standard solution, sample solution, the sample solution, the order of standard solution.

4.4.6 Computing

Sample HAP (DAP) the mass fraction 2 (mg/kg), according to formula (2).

2 = A2

104 (2)

Where.

A1 --- the standard solution, the average HAP (DAP) peak area;

A2 --- sample solution, the average HAP (DAP) peak area;

--- standard samples HAP (DAP) mass fraction, expressed in%;

500 --- standard dilution.

4.4.7 Allows poor

Determination results parallel relative deviation should not exceed 30%, and the arithmetic mean value as a measurement result.

Carried out in GB/T 1601.

4.6 Determination of loss on drying

4.6.1 Instruments

Oven. 105 °C ± 2 °C;

Weighing bottle. an inner diameter of 70mm, 40mm high;

Dryer.

4.6.2 Determination Step

The weighing bottle placed in an oven bake IH, placed in a desiccator taken cooled to room temperature, weigh (accurate to 0.0002g). Repeating the above steps Step, until a constant weight weighing bottle. 2g sample was placed in the bottle, paving, weighed (accurate to 0.01g), the weighing bottle placed in an oven, without Cap, post-baking IH, removed and placed in a desiccator to cool to room temperature, weigh (accurate to 0.0002g).

4.6.3 Computing

The mass fraction of the sample 3 Loss on drying (%), according to equation (3) is calculated.

Where.

4.6.4 Allows poor

The measurement results of the two parallel relative deviation should not exceed 30%; and the arithmetic mean as a measurement result.

4.7 Product testing and acceptance

Shall comply with the provisions of GB/T 1604's. Process limit values using rounding value comparison method.