Oxazolam 1193

JP XVI Official Monographs / Oxazolam 1193

Assay Weigh accurately about 0.5 g of Oxaprozin, previ- Oxazolam in ethanol (95) (1 in 100,000) as directed under ously dried, dissolve in 50 mL of ethanol (95), and titrate Ultraviolet-visible Spectrophotometry <2.24>,andcompare <2.50> with 0.1 mol/L sodium hydroxide VS (potentiometric the spectrum with the Reference Spectrum: both spectra titration). Perform a blank determination, and make any exhibit similar intensities of absorption at the same wave- necessary correction. lengths. (5) Proceed with Oxazolam as directed under Flame Each mL of 0.1 mol/L sodium hydroxide VS Coloration Test <1.04> (2), and perform the test: a green ＝ 29.33 mg of C H NO 18 15 3 color appears. Containers and storage Containers—Tight containers. Absorbance <2.24> E1z (246 nm): 410 – 430 (after drying, Storage—Light-resistant. 1cm 1 mg, ethanol (95), 100 mL). Purity (1) Chloride <1.03>—To 1.0 g of Oxazolam add 50 Oxazolam mL of water, allow to stand for 1 hour with occasional shak- ing, and filter. To 25 mL of this filtrate add 6 mL of dilute オキサゾラム nitric acid and water to make 50 mL, and perform the test using this solution as the test solution. Prepare the control solution with 0.20 mL of 0.01 mol/L hydrochloric acid VS (not more than 0.014z). (2) Heavy metals <1.07>—Proceed with 1.0 g of Oxazol- am according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 20 ppm).

C18H17ClN2O2:328.79 (3) Arsenic <1.11>—Place 1.0 g of Oxazolam in a Kjel- 10-Chloro-2-methyl-11b-phenyl-2,3,7,11b- dahl flask, add 5 mL of sulfuric acid and 5 mL of nitric acid, tetrahydro[1,3]oxazolo[3,2-d][1,4]benzodiazepin- and heat gently. Repeat the addition of 2 to 3 mL of nitric 6(5H)-one acid at times, and continue to heat until a colorless to light [24143-17-7] yellow solution is obtained. After cooling, add 15 mL of saturated ammonium oxalate monohydrate solution, heat Oxazolam, when dried, contains not less than the solution until dense white fumes are evolved, and evapo- 99.0z of C18H17ClN2O2. rate to a volume of 2 to 3 mL. After cooling, dilute with waterto10mL,andperformthetestwiththissolutionas Description Oxazolam occurs as white crystals or crystal- the test solution (not more than 2 ppm). line powder. (4) Related substances—Dissolve 0.05 g of Oxazolam in It is odorless and tasteless. 10 mL of dichloromethane, and use this solution as the It is freely soluble in acetic acid (100), soluble in 1,4- sample solution. Pipet 1 mL of the sample solution, add dioxane and in dichloromethane, slightly soluble in ethanol dichloromethane to make exactly 200 mL, and use this solu- (95) and in diethyl ether, and practically insoluble in water. tion as the standard solution. Perform the test with these so- It dissolves in dilute hydrochloric acid. lutions as directed under Thin-layer Chromatography <2.03>. It gradually changes in color by light. Spot 10 mL each of the sample solution and standard solu- Melting point: about 1879C (with decomposition). tion on a plate of silica gel with fluorescent indicator for Identification (1) Dissolve 0.01 g of Oxazolam in 10 mL thin-layer chromatography. Immediately air-dry, develop of ethanol (95) by heating, and add 1 drop of hydrochloric the plate with a mixture of toluene and acetone (8:1) to a dis- acid: a light yellow color develops, and the solution shows a tance of about 10 cm, and air-dry the plate. Examine under yellow-green fluorescence under ultraviolet light (main wave- ultraviolet light (main wavelength: 254 nm): the spots other length: 365 nm). Add 1 mL of sodium hydroxide TS to this than the principal spot from the sample solution are not solution: the color and fluorescence of this solution disap- more intense than the spot from the standard solution. pear immediately. Loss on drying <2.41> Not more than 0.5z (1 g, 1059C, (2) Dissolve 0.01 g of Oxazolam in 5 mL of dilute hydro- 3 hours). chloric acid by heating in a water bath for 10 minutes. After cooling, 1 mL of this solution responds to the Qualitative Residue on ignition <2.44> Not more than 0.1z (1 g). Tests <1.09> for primary aromatic amines. Assay Weigh accurately about 0.65 g of Oxazolam, previ- (3) Place 2 g of Oxazolam in a 200-mL flask, add 50 mL ously dried, dissolve in 100 mL of a mixture of acetic acid of ethanol (95) and 25 mL of 6 mol/L hydrochloric acid TS, (100) and 1,4-dioxane (1:1). Titrate <2.50> with 0.1 mol/L and boil under a reflux condenser for 5 hours. After cooling, perchloric acid VS until the color of the solution changes neutralize with a solution of sodium hydroxide (1 in 4), and from purple through blue to blue-green (indicator: 2 drops extract with 30 mL of dichloromethane. Dehydrate with 3 g of crystal violet TS). Perform a blank determination, and of anhydrous sodium sulfate, filter, and evaporate the make any necessary correction. dichloromethane of the filtrate. Dissolve the residue in 20 mL of methanol by heating on a water bath, and cool imme- Each mL of 0.1 mol/L perchloric acid VS diately in an ice bath. Collect the crystals, and dry in vacuum ＝ 32.88 mg of C18H17ClN2O2 at 609C for 1 hour: the crystals melt <2.60> between 969C Containers and storage Containers—Tight containers. and 1009C. Storage—Light-resistant. (4) Determine the absorption spectrum of a solution of 1194 Oxethazaine / Official Monographs JP XVI

methanol to make exactly 10 mL, then add 0.1 mL of a solu- Oxethazaine tion of 1-fluoro-2,4-dinitrobenzene in methanol (1 in 25), shake well, and heat at 609C for 20 minutes: the solution has Oxetacaine no more color than the following control solution. Control solution: To 0.10 g of 2-aminoethanol add metha- オキセサゼイン nol to make exactly 200 mL, pipet 1 mL of this solution, and add methanol to make exactly 10 mL. Proceed as directed above. Loss on drying <2.41> Not more than 0.5z (1 g, in vacu- um, 609C, 3 hours). Residue on ignition <2.44> Not more than 0.1z (1 g). C H N O : 467.64 28 41 3 3 Assay Weigh accurately about 0.9 g of Oxethazaine, previ- 2,2?-(2-Hydroxyethylimino)bis[N-(1,1-dimethyl-2- ously dried, dissolve in 50 mL of acetic acid (100), and titrate phenylethyl)-N-methylacetamide] <2.50> with 0.1 mol/L perchloric acid VS (indicator: 2 drops [126-27-2] of crystal violet TS). Perform a blank determination, and make any necessary correction. Oxethazaine, when dried, contains not less than 98.5z of C28H41N3O3. Each mL of 0.1 mol/L perchloric acid VS ＝ 46.76 mg of C H N O Description Oxethazaine occurs as a white to pale yellow- 28 41 3 3 ish white, crystalline powder. Containers and storage Containers—Tight containers. Identification (1) Determine the absorption spectrum of a solution of Oxethazaine in ethanol (95) (1 in 2500) as di- rected under Ultraviolet-visible Spectrophotometry <2.24>, Oxprenolol Hydrochloride and compare the spectrum with the Reference Spectrum: オクスプレノロール塩酸塩 both spectra exhibit similar intensities of absorption at the same wavelengths. (2) Determine the infrared absorption spectrum of Oxethazaine as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>,andcom- pare the spectrum with the Reference Spectrum: both spectra C H NO .HCl: 301.81 exhibits similar intensities of absorption at the same wave 15 23 3 (2RS)-1-[2-(Allyloxy)phenoxy]- numbers. 3-(1-methylethyl)aminopropan-2-ol monohydrochloride Melting point <2.60> 101–1049C. [6452-73-9] Purity (1) Chloride <1.03>—Dissolve 1.0 g of Oxetha- Oxprenolol Hydrochloride, when dried, contains zaine in 20 mL of ethanol (95), add 6 mL of dilute nitric acid not less than 98.5z of C H NO .HCl. and water to make 50 mL. Perform the test using this solu- 15 23 3 tion as the test solution. Prepare the control solution with Description Oxprenolol Hydrochloride occurs as a white, 0.30 mL of 0.01 mol/L hydrochloric acid VS, 20 mL of crystalline powder. ethanol (95), 6 mL of dilute nitric acid and water to make 50 It is very soluble in water, freely soluble in ethanol (95) mL (not more than 0.011z). and in acetic acid (100), slightly soluble in acetic anhydride, (2) Heavy metals <1.07>—Proceed with 2.0 g of Oxetha- and practically insoluble in diethyl ether. zaine according to Method 2, and perform the test. Prepare Identification (1) To 2 mL of a solution of Oxprenolol the control solution with 2.0 mL of Standard Lead Solution Hydrochloride (1 in 100) add 1 drop of copper (II) sulfate TS (not more than 10 ppm). and 2 mL of sodium hydroxide TS: a blue-purple color de- (3) Related substances—Dissolve 0.40 g of Oxethazaine velops. To this solution add 1 mL of diethyl ether, shake in 10 mL of ethanol (95), and use this solution as the sample well, and allow to stand: a red-purple color develops in the solution. Pipet 1 mL of the sample solution, add ethanol (95) diethyl ether layer, and a blue-purple color develops in the to make exactly 100 mL, and use this solution as the stand- water layer. ard solution. Perform the test with these solutions as di- (2) To 3 mL of a solution of Oxprenolol Hydrochloride rected under Thin-layer Chromatography <2.03>. Spot 10 mL (1 in 150) add 3 drops of Reinecke salt TS: a light red pre- each of the sample solution and standard solution on a plate cipitate is formed. of silica gel with fluorescent indicator for thin-layer chroma- (3) Determine the infrared absorption spectrum of Ox- tography. Develop the plate with a mixture of isopropyl- prenolol Hydrochloride, previously dried, as directed in the ether, tetrahydrofuran, methanol and ammonia solution (28) potassium chloride disk method under Infrared Spectropho- (24:10:5:1) to a distance of about 10 cm, and air-dry the tometry <2.25>, and compare the spectrum with the Refer- plate. Examine under ultraviolet light (main wavelength: 254 ence Spectrum: both spectra exhibit similar intensities of ab- nm): the spots other than the principal spot from the sample sorption at the same wave numbers. solution are not more intense than the spot from the stand- (4) A solution of Oxprenolol Hydrochloride (1 in 50) re- ard solution. sponds to the Qualitative Tests <1.09> for chloride. (4) 2-Aminoethanol—To 1.0 g of Oxethazaine add