Doxapram Hydrochloride
;)
2-Pyrrolidinone,1-ethyl-4-[2-(4-morpholinyl)ethyl]-3,3-diphenyl-,monohydrochloride,monohydrate,(±)-.
(±)-1-Ethyl-4-(2-morpholinoethyl)-3,3-diphenyl-2-pyrrolidinone monohydrochloride monohydrate [7081-53-0].
Anhydrous 414.98 [113-07-5].
»Doxapram Hydrochloride,dried at 105
for 2hours,contains not less than 98.0percent and not more than 100.5percent of C24H30N2O2·HCl.
for 2hours,contains not less than 98.0percent and not more than 100.5percent of C24H30N2O2·HCl.
Packaging and storage—
Preserve in tight containers.
Identification—
A:
Infrared Absorption á197Kñ.
Solution:
400µg per mL.
Medium:
water.
Absorptivities at 258nm,calculated on the dried basis,do not differ by more than 3.0%.
pHá791ñ:
between 3.5and 5.0,in a solution (1in 100).
Loss on drying á731ñ—
Dry it at 105for 2hours:it loses between 3.0%and 4.5%of its weight.
for 2hours:it loses between 3.0%and 4.5%of its weight.
Residue on ignition á281ñ:
not more than 0.3%.
Heavy metals,Method IIá231ñ:
0.002%.
Chromatographic purity—
Dragendorff reagent—
Dissolve 17g of bismuth subnitrate and 200g of tartaric acid in 800mLof water (Solution A).Dissolve 160g of potassium iodide in 400mLof water (Solution B).Mix Solution Aand Solution B.To 25mLof this stock solution add 50g of tartaric acid and 250mLof water,and mix.
Test preparation—
Dissolve 57mg of Doxapram Hydrochloride in 0.5mLof 0.1Nsodium hydroxide,add 1.0mLof chloroform,and shake.
Standard preparation A—
Dissolve 57mg of USP Doxapram Hydrochloride RSin 0.5mLof 0.1Nsodium hydroxide,add 1.0mLof chloroform,and shake.
Standard preparation B—
Dissolve 11.4mg of USP Doxapram Hydrochloride RSin 0.5mLof 0.1Nsodium hydroxide,add 100mLof chloroform,and shake.
Procedure—
Apply 10-µLportions of the chloroform solutions obtained from the Test preparationand the Standard preparationsto a suitable thin-layer chromatographic plate (see Chromatography á621ñ)coated with a 0.25-mm layer of chromatographic silica gel mixture.Allow the spots to dry,and develop the chromatogram in a chromatographic chamber lined with paper and equilibrated with a solvent system consisting of a mixture of isopropyl alcohol and 1Nammonium hydroxide (4:1)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,and allow the solvent to evaporate.Spray the plate with Dragendorff reagentin order to visualize the spots:the RFvalue of the principal spot obtained from the Test preparationcorresponds to that obtained from Standard preparation A,and no spot,other than the principal spot,in the chromatogram of the Test preparationis larger or more intense than the principal spot obtained from Standard preparation B(0.2%).
Assay—
Dissolve about 800mg of Doxapram Hydrochloride,previously dried and accurately weighed,in 50mLof glacial acetic acid,add 1drop of crystal violet TSand 10mLof mercuric acetate TS,and titrate with 0.1Nperchloric acid VSto a blue-green endpoint.Perform a blank determination,and make any necessary correction.Each mLof 0.1Nperchloric acid is equivalent to 41.50mg of C24H30N2O2·HCl.
Auxiliary Information—
Staff Liaison:Salvador C.Salado,M.S.,Scientist and Latin American Liaison
Expert Committee:(PA3)Pharmaceutical Analysis 3
USP28–NF23Page 692
Pharmacopeial Forum:Volume No.29(6)Page 1874
Phone Number:1-301-816-8165