GB 22169-2008Fomesafen aqueous solution (English PDF)

3.1 Composition and appearance

This product should be compliant fomesafen original drug is made, the appearance of a homogeneous liquid, no suspended solids and sediment.

3.2 Technical Specifications

Fomesafen agent shall comply with the requirements of Table 1.

Table 1 fomesafen agent control program indicators

project

index

250g/L 25%

Fomesafen mass fraction a /% or concentration (20 °C) / (g/L) 22.0 + 1.3-1.3 + 15-15 250 25.0 + 1.5-1.5 Water insoluble /% <= 0.3 pH range of 6.0 to 9.0 Dilution stability (20 times) Qualified Low temperature stability Qualified b Thermal storage stability b qualified when a dispute arises, to fomesafen mass fraction of arbitration.

B when normal production, low-temperature storage stability and thermal stability test at least every three months, once measured.

Test Method 4

4.1 Sampling

According to GB/T 1605-2001 in "liquid formulations sampling" approach. Determining sample package using a random number table method; the final sample size not less than 250mL.

4.2 Identification Test

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

4.3 Determination of fomesafen mass fraction

4.3.1 Method summary

Sample was dissolved in methanol, + water + phosphoric acid as the mobile phase, to use as filler HypersilODS stainless steel column and ultraviolet detection Detector (230nm), the sample of fomesafen reverse phase high performance liquid chromatography, external standard.

4.3.2 Reagents and solutions

Methanol. HPLC grade;

Phosphoric acid;

Water. The new secondary steam distilled water;

Fomesafen Sample. Known fomesafen mass fraction >=98.0%.

4.3.3 Instruments

High performance liquid chromatography. a variable wavelength UV detector;

Chromatographic data processor;

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

Filter. pore size of about 0.45µm;

Micro injector. 50µL;

Quantitative sample line. 5µL;

Ultrasonic cleaner.

4.3.4 HPLC operating conditions

Mobile phase. [Psi] (methanol. water. phosphoric acid) = 600.400.0.2, filtered through a filter membrane and degassed;

Flow rate. 1.0mL/min;

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

Detection wavelength. 230nm;

Injection volume. 5µL;

Retention time. fomesafen 7.8min.

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 fomesafen agent HPLC is shown in Figure 1.

1 --- fomesafen.

1 fomesafen agent HPLC diagram of FIG.

4.3.5 Measuring step

4.3.5.1 Preparation of standard solution

Weigh fomesafen standard 0.1g (accurate to 0.0002g), a 50mL volumetric flask, dissolved in methanol and diluted to the mark, Shake well. Pipette accurately pipette 5mL above solution was placed in another 50mL volumetric flask, diluted with methanol to the mark.

4.3.5.2 Preparation of sample solution

Weigh fluorine fomesafen 0.1g (accurate to 0.0002g) sample, placed in 50mL volumetric flask, dilute to the mark with methanol, shake uniform. Pipette accurately pipette 5mL above solution was placed in another 50mL volumetric flask, diluted with methanol 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 fomesafen relative peak area After the change is less than 1.0%, according to the solution, the sample solution, the sample solution and standard sequence of the standard solution was measured.

4.3.6 Calculation

The two needle sample solution measured before and after the peak area of the sample and two doses of the standard solution of fomesafen were averaged. Specimen (1) Calculation fomesafen mass fraction of 1 (%) according to the formula; (2) to calculate the concentration of rho1 (g/L) by the formula.

1 = A2

rho1 =

10 (2)

Where.

A1 --- the standard solution, the average fomesafen peak area;

A2 --- sample solution, the average fomesafen peak area;

--- Standard samples fomesafen mass fraction, expressed as a percentage;

Density rho --- 20 °C when the sample in grams per milliliter (g/mL) (according to GB/T 4472 of "density meter method" Determination).

4.3.7 Allowable difference

Fomesafen concentration, poor concentration measurement results of two parallel, should not exceed 0.8%, respectively, 8g/L, whichever is the arithmetic Mean as a measurement result.

4.4 Determination of insoluble matter

4.4.1 Method summary

Samples dissolved in water, all insolubles were filtered off, dried weighed.

4.4.2 Instruments

Weighing bottle;

Glass sand core crucible. 3 #;

Oven. 105 °C ± 2 °C.

4.4.3 Measuring step

In an oven, the glass sand core crucible and dried to constant weight (accurate to 0.0002g), a sample was weighed 20g (accurate to 0.01g), placed 100mL beaker, rinsed with 200mL of water transferred into a measuring cylinder, stoppered, shaken violently, so that all dissolved solubles. The solution After the crucible filtration, washed with distilled water residue in the crucible, each with 25mL, washed three times total. Setting the crucible and the residue was oven at 105 °C Dried to constant weight (accurate to 0.0002g), then cool to room temperature, and weighed.

The mass fraction of water-insoluble 2 (%) according to equation (3) Calculated.

Where.

According to GB/T 1601 carried out.

4.6 Dilution stability test

4.6.1 Reagents and Instruments

Standard hard water. rho (Mg 2 ++ Ca2 +) = 342mg/L;

Cylinder. 100mL;

Water bath. 30 °C ± 2 °C;

Pipette. 5mL.

4.6.2 Test procedure

With pipette 5mL sample, placed in 100mL measuring cylinder and diluted to the mark with standard hard water, and mix. Add this cylinder thermostat Water bath, allowed to stand for 1h. As dilution uniform, no precipitation was qualified.

4.7 Low temperature stability test

According to GB/T 19137 in "homogeneous emulsion and liquid preparations" to. Volume precipitated solid or oil does not exceed 0.3mL qualified.

4.8 Thermal storage stability test

According to GB/T 19136 in "liquid formulation" to. After the thermal storage, fomesafen content should not be less than 95% of the heat storage before; dilution stable Qualitative should still meet the requirements of 3.2.

4.9 Product testing and acceptance

Shall comply with GB/T 1604's. Limit numerical processing using rounding value comparison method.