Loxapine Succinate
C18H18ClN3O·C4H6O4 445.90

Butanedioic acid,compd.with 2-chloro-11-(4-methyl-1-piperazinyl)dibenz[b,f][1,4]oxazepine(1:1).
2-Chloro-11-(4-methyl-1-piperazinyl)dibenz[b,f][1,4]oxazepine succinate (1:1) [27833-64-3].
»Loxapine Succinate contains not less than 98.5percent and not more than 101.0percent of C18H18ClN3O·C4H6O4,calculated on the dried basis.
Packaging and storage— Preserve in tight containers.
Identification—
A: Infrared Absorption á197Kñ.
B: Ultraviolet Absorption á197Uñ
Solution: 20µg per mL.
Medium: 0.01Nhydrochloric acid.
Melting range,Class Iá741ñ: between 150and 153.
Loss on drying á731ñ Dry it at 105for 4hours:it loses not more than 0.5%of its weight.
Residue on ignition á281ñ: not more than 0.1%.
Chromatographic purity—
Standard preparations— Dissolve USP Loxapine Succinate RSin methanol and mix to obtain Standard preparation Ahaving a known concentration of 0.5mg per mL.Dilute portions of Standard preparation Aquantitatively with methanol to obtain Standard preparation Band Standard preparation Chaving known concentrations of 0.25mg per mLand 0.1mg per mL,respectively.
Test preparation— Dissolve an accurately weighed quantity of Loxapine Succinate in methanol to obtain a solution containing 50mg per mL.
Procedure— Separately apply 5µLof the Test preparationand each of the three Standard preparationsto a suitable high performance thin-layer chromatographic plate (see Chromatography á621ñ)coated with a 0.10-mm layer of chromatographic silica gel mixture.Allow the spots to dry,and develop the chromatogram in a solvent system consisting of a mixture of ethyl acetate,methanol,and ammonium hydroxide (9:1:0.1)until the solvent front has moved about three-fourths of the length of the plate.Remove the plate from the developing chamber,mark the solvent front,air-dry,examine the plate under short-wavelength UVlight,and compare the intensities of any secondary spots observed in the chromatogram of the Test preparationwith those of the principal spots in the chromatograms of the Standard preparations:no secondary spot from the chromatogram of the Test preparationis larger or more intense than the principal spot obtained from Standard preparation A(1.0%),and the sum of the intensities of the secondary spots obtained from the Test preparationcorresponds to not more than 2.0%.
Organic volatile impurities,Method Vá467ñ: meets the requirements.
Solvent— Use dimethyl sulfoxide.
Assay— Dissolve about 400mg of Loxapine Succinate,accurately weighed,in 80mLof glacial acetic acid,and titrate with 0.1Nperchloric acid VS,determining the endpoint potentiometrically.Perform a blank determination,and make any necessary correction.Each mLof 0.1Nperchloric acid is equivalent to 22.29mg of C18H18ClN3O·C4H6O4.
Auxiliary Information— Staff Liaison:Salvador C.Salado,M.S.,Scientist and Latin American Liaison
Expert Committee:(PA3)Pharmaceutical Analysis 3
USP28–NF23Page 1158
Phone Number:1-301-816-8165