Permethrin (25:75)

(Ph. Eur. monograph 1762)

C₂₁H₂₀Cl₂O₃ 391.3 Undefined cis/trans ratio 52645-53-1

Action and use

Insecticide.

DEFINITION

Mixture of the cis and trans isomers of (3-phenoxyphenyl)methyl (1RS,2RS)-2-(2,2-dichloroethenyl)-3,3-dimethylcyclopropane-1-carboxylate.

Content

— total: 98.0 per cent to 102.0 per cent (anhydrous substance);

— cis isomer: 23.0 per cent to 27.0 per cent (anhydrous substance);

— trans isomer: 73.0 per cent to 77.0 per cent (anhydrous substance).

CHARACTERS

Appearance

Colourless or slightly brownish viscous liquid, semi-solid or crystalline solid.

Solubility

Practically insoluble in water, very soluble in heptane, freely soluble in anhydrous ethanol, sparingly soluble in ethylene glycol.

IDENTIFICATION

A. Infrared absorption spectrophotometry (2.2.24).

Comparison: permethrin (25:75) CRS.

B. Examine the chromatograms obtained in the assay.

Results: The 2 principal peaks in the chromatogram obtained with the test solution are similar in retention time and in cis/trans ratio to the 2 principal peaks in the chromatogram obtained with the reference solution (cis/trans ratio = about 0.3).

TESTS

Gas chromatography (2.2.28): use the normalisation procedure.

Test solution: Warm the substance to be examined at 70-85 °C for 20 min. Dissolve 1.0 g of this substance in heptane R and dilute to 20.0 mL with the same solvent.

Reference solution (a): Dissolve 50 mg of permethrin for system suitability CRS (containing impurities B, C and G) in heptane R and dilute to 1.0 mL with the same solvent.

Reference solution (b): Dilute 1.0 mL of the test solution to 100.0 mL with heptane R. Dilute 1.0 mL of this solution to 20.0 mL with heptane R.

Column:

— material: fused silica;

— size: l = 15 m, Ø = 0.53 mm;

— stationary phase: methylpolysiloxane R (film thickness 1.5 μm).

Carrier: gas nitrogen for chromatography R.

Flow rate: 12.0 mL/min.

Split ratio: 1:10.

Temperature:

	Time (min)	Temperature (°C)
Column	0 – 2	45
	2 – 26.5	45 → 290
	26.5 – 40.5	290
Injection port		250
Detector		290

Detection: Flame ionisation.

Injection: 1 μL.

Identification of impurities: Use the chromatogram supplied with permethrin for system suitability CRS and the chromatogram obtained with reference solution (a) to identify the peaks due to impurities B, C and G.

Relative retention: With reference to permethrin (retention time = about 24 min): impurity B = about 0.5; impurity C = about 0.7; impurity G = about 0.9.

System suitability: Reference solution (a):

— resolution: minimum 2.0 between the peaks due to impurity G and permethrin.

Limits:

— correction factor: for the calculation of content, multiply the peak area of impurity B by 1.5;

— impurities B, C: for each impurity, maximum 0.15 per cent;

— unspecified impurities: for each impurity, maximum 0.10 per cent;

— total: maximum 0.5 per cent;

— reporting threshold: 0.05 per cent (reference solution (b)).

Water (2.5.32)

Maximum 0.25 per cent, determined on 0.100 g using the evaporation technique:

— temperature: 110 °C;

— heating time: 3 min.

Sulfated ash (2.4.14)

Maximum 0.1 per cent, determined on 1.0 g.

ASSAY

Liquid chromatography (2.2.29).

Test solution: Warm the substance to be examined at 70-85 °C for 20 min. Dissolve 0.100 g of this substance in the mobile phase using sonication and dilute to 50.0 mL with the mobile phase.

Reference solution: Warm permethrin (25:75) CRS at 70-85 °C for 20 min. Dissolve 0.100 g of this substance in the mobile phase using sonication and dilute to 50.0 mL with the mobile phase.

Column:

— size: l = 0.25 m, Ø = 4.6 mm;

— stationary phase: silica gel for chromatography R (5 μm);

— temperature: 30 °C.

Mobile phase: dioxan R, heptane R (1.1:98.9 V/V).

Flow rate: 1.2 mL/min.

Detection: Spectrophotometer at 280 nm.

Injection: 20 μL.

Run time: Twice the retention time of cis-permethrin.

Retention time: cis-permethrin = about 6 min.

Elution order: cis-permethrin, trans-permethrin.

System suitability: Reference solution:

— resolution: minimum 2.0 between the peaks due to cis-permethrin and trans-permethrin.

Calculation of percentage contents:

— calculate the percentage content of cis-permethrin and trans-permethrin by normalisation;

— calculate the percentage content of C₂₁H₂₀Cl₂O₃ taking into account the assigned content ofpermethrin (25:75) CRS.

STORAGE

Protected from light.

IMPURITIES

Specified impurities B, C.

Other detectable impurities (the following substances would, if present at a sufficient level, be detected by one or other of the tests in the monograph. They are limited by the general acceptance criterion for other/unspecified impurities and/or by the general monograph Substances for pharmaceutical use (2034). It is therefore not necessary to identify these impurities for demonstration of compliance. See also 5.10. Control of impurities in substances for pharmaceutical use) A, D, E, F, G, H.

Permethrin