C9H9Cl2N3·HCl 266.55

Benzenamine,2,6-dichloro-N-2-imidazolidinylidene-,monohydrochloride.
2-[(2,6-Dichlorophenyl)imino]imidazolidine monohydrochloride [4205-91-8].

Packaging and storage— Preserve in tight containers.Store at 25,excursions permitted between 15and 30.

USP Reference standards á11ñ— USP Clonidine Hydrochloride RS.

Identification—

pHá791ñ: between 3.5and 5.5,in a solution (1in 20).

Loss on drying á731ñ— Dry it at 105to constant weight:it loses not more than 0.5%of its weight.

Residue on ignition á281ñ: not more than 0.1%.

Chromatographic purity— Dissolve 200mg in methanol,and dilute with methanol to 2.0mLto obtain the test solution.Dissolve a suitable quantity of USP Clonidine Hydrochloride RSin methanol to obtain a Standard solution having a known concentration of 100mg per mL.Dilute a portion of this solution quantitatively and stepwise with methanol to obtain a diluted Standard solution having a concentration of 100µg per mL.Apply separate 2-µLportions of the test solution,the Standard solution,and the diluted Standard solution to a suitable thin-layer chromatographic plate (see Chromatography á621ñ)coated with a 0.25-mm layer of chromatographic silica gel mixture.Develop the chromatogram in a freshly prepared solvent system consisting of a mixture of toluene,dioxane,dehydrated alcohol,and ammonium hydroxide (10:8:2:1),until the solvent front has moved three-fourths of the length of the plate.Remove the plate from the chamber,allow the solvent to evaporate,and dry it at 100for 1hour.Dip the plate into a dipping chamber filled to three-fourths of its height with sodium hypochlorite solution,diluted to contain 0.5%available chlorine,dry in a fume hood with a current of air for 1hour,and spray with starch-potassium iodide TS:the RFvalue of the principal spot from the test solution corresponds to that of the Standard solution.Any other spot obtained from the test solution does not exceed,in size or intensity,the principal spot obtained from the diluted Standard solution (0.1%),and the total of any spots does not exceed 0.2%.

Assay— Dissolve about 200mg of Clonidine Hydrochloride,accurately weighed,in about 80mLof glacial acetic acid,add 15mLof mercuric acetate TS,and titrate with 0.1Nperchloric acid VS,determining the endpoint potentiometrically,using a glass electrode and a sleeve-type calomel electrode containing 0.1Nlithium perchlorate in glacial acetic acid (see Titrimetry á541ñ).Perform a blank determination,and make any necessary correction.Each mLof 0.1Nperchloric acid is equivalent to 26.66mg of C9H9Cl2N3·HCl.

Expert Committee:(PA5)Pharmaceutical Analysis 5

USP28–NF23Page 513

Phone Number:1-301-816-8305