GB 23552-2009Thiophanate-methyl wettable powders (English PDF)

3.1 Composition and appearance

This product should meet the criteria of thiophanate-methyl of the drug and appropriate processing auxiliaries and fillers are made as loose powder uniformly, there should be Clumps.

3.2 Technical Specifications

Thiophanate-methyl wettable powder should meet the requirements of Table 1.

Table benomyl wettable powder Item Index 1 control methylsulfanyl

project

index

70% 50%

Thiophanate-methyl mass fraction /% 70.0 + 50.0 + 2.5-2.5 2.5-2.5 HAP (2- amino-3-hydroxy-phenazine) mass fraction a/(mg/kg) <= 0.4 0.3 DAP (2,3- diamino phenazine) mass fraction a/(mg/kg) <= 4.0 3.0 pH range 6.0 to 9.0 Fineness (45µm standard sieve) /% >= 98 Suspension rate /% >= 70 Wetting time/s <= 90 Thermal storage stability test a /% passing when a normal production, the mass fraction of HAP, the mass fraction of the DAP, the thermal storage stability test for detecting at least every 3 months once.

Test Method 4

4.1 Sampling

Carried out in GB/T 1605-2001 of "solid preparation sampling" approach. Determining Sample packages with a random number table method; final sample size not less than 300g.

4.2 Identification Test

HPLC --- This identification test can be conducted simultaneously measuring the mass fraction of benomyl and thiophanate-methyl. In the same chromatographic operating conditions the lower member, and the retention time of peaks benomyl solution of methylthio the retention time of a standard sample peak relative difference in the sample solution should be 1.5% or less.

When using the above method of identification of active components in doubt, other effective means may be employed for authentication.

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. [Phi] (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 10.4min.

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 wettable powder shown in Figure 1 HPLC.

1 --- thiophanate-methyl.

Figure 1 HPLC thiophanate-methyl wettable powder

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.

4.3.5 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. A pipetted sample solution was diluted to 5mL above another in 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 1.0%, 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 0.1mg/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. HAP known mass fraction >=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. [Phi] (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 3.3min; DAP about 7.5min.

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.

HAP, DAP standard sample by HPLC is shown in Figure 2, thiophanate-methyl wettable powders HAP, DAP measured by HPLC Shown in Figure 3.

1 --- HAP;

2 --- DAP.

FIG 2 HAP and DAP standard liquid chromatography FIG.

1 --- HAP;

2 --- DAP.

HPLC FIG. 3 thiophanate-methyl wettable powder and HAP DAP assay

4.4.5 Determination Step

4.4.5.1 Preparation of standard solution

4.4.5.1.1 DAP Preparation of standard solution (A 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, the standby (the solution was stable for 2 months at dark at 4 °C conditions).

4.4.5.1.2 HAP Preparation of standard solution (B solution)

Sample HAP accurately weighed 0.015 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, the standby (the solution was stable for 2 months at dark at 4 °C conditions).

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 solutions Solution to be prepared before use).

4.4.5.2 Preparation of sample solution

20.0 g of accurately weighed (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. And then filtered at 3000 rpm/min centrifuge 5min, the supernatant.

4.4.5.3 Determination

Under the above operating conditions, after the instrument is stable, the number of consecutive doses of the standard solution is injected until the two adjacent needles HAP, the DAP relative peak area After 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 fineness

According to GB/T 16150 in the "wet sieve method".

4.7 Determination of the suspension rate

According to GB/T 14825 carried out. Weigh 0.35g sample containing thiophanate methyl (accurate to 0.0002g). 50mL methanol with an amount of the remaining 25mL cylinder suspension and the precipitate was all transferred to 100mL volumetric flask to volume with methanol, shaken at ultrasonic 3min, shake, filtration. 4.3 Determination by mass spirit thiophanate-methyl, calculate suspensibility.

4.8 Determination of wetting time

Carried out in GB/T 5451.

Thermal storage stability test 4.9 According to GB/T 19136 of "powder formulation" performed. After the heat storage, thiophanate-methyl content should be greater than the measured mass fraction before hot storage 97% was still the suspension should meet standard requirements.

4.10 Product inspection and acceptance

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