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Quinidine Sulfate Hydrate / O‹Cial Monographs JP XV

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Quinidine Sulfate Hydrate / O‹Cial Monographs JP XV 1050 Quinidine Sulfate Hydrate / O‹cial Monographs JP XV Weigh accurately an amount of Pyrrolnitrin and Pyrrolnitrin less than 98.5z of quinidine sulfate [(C20H24N2O2)2.H2 Reference Standard, equivalent to about 50 mg (potency), SO4:746.91]. dissolve in diluted acetonitrile (3 in 5) to make exactly 50 mL. Description Quinidine Sulfate Hydrate occurs as white Pipet 10 mL each of these solutions, add exactly 10 mL of the crystals. It is odorless, and has a very bitter taste. internal standard solution, add diluted acetonitrile (3 in 5) to It is freely soluble in ethanol (95) and in boiling water, make 100 mL, and use these solutions as the sample solution sparingly soluble in water, and practically insoluble in diethyl and standard solution. Perform the test with 5 mLeachofthe ether. Quinidine Sulfate Hydrate, previously dried, is freely sample solution and standard solution as directed under Liq- soluble in chloroform. uid Chromatography <2.01> according to the following con- It darkens gradually by light. ditions, and determine the ratios, Q and Q , of the peak T S Optical rotation [a]20: ＋275 – ＋2879(after drying, 0.5 g, area of pyrrolnitrin to that of the internal standard. D 0.1 molWL hydrochloric acid VS, 25 mL, 100 mm). Amount [ mg (potency)] of C H Cl N O 10 6 2 2 2 Identiˆcation (1) Dissolve 0.01 g of Quinidine Sulfate Hy- ＝W ×(Q /Q )×1000 S T S drate in 10 mL of water and 2 to 3 drops of dilute sulfuric WS: Amount [mg (potency)] of Pyrrolnitrin Reference acid: a blue ‰uorescence is produced. Standard (2) To 5 mL of an aqueous solution of Quinidine Sulfate Hydrate (1 in 1000) add 1 to 2 drops of bromine TS, then add Internal standard solution—A solution of benzyl benzoate in 1 mL of ammonia TS: a green color develops. diluted acetonitrile (3 in 5) (3 in 500). (3) To 5 mL of an aqueous solution of Quinidine Sulfate Operating conditions— Hydrate(1in100)add1mLofsilvernitrateTS,stirwithag- Detector: An ultraviolet absorption photometer lass rod, and allow to stand for a short interval: a white (wavelength: 254 nm). precipitate is produced, and it dissolves on addition of nitric Column: A stainless steel column 4 mm in inside diameter acid. and 15 cm in length, packed with octylsilanized silica gel for (4) Dissolve 0.4 g of Quinidine Sulfate Hydrate in 20 mL liquid chromatography (5 mm in particle diameter). of water and 1 mL of dilute hydrochloric acid: the solution Column temperature: A constant temperature of about responds to the Qualitative Tests <1.09> for sulfate. 259C. Mobile phase: A mixture of water and acetonitrile (11:9). pH <2.54> Dissolve 1.0 g of Quinidine Sulfate Hydrate in Flow rate: Adjust the ‰ow rate so that the retention time of 100 mL of freshly boiled and cooled water: the pH of this so- pyrrolnitrin is about 9 minutes. lution is between 6.0 and 7.0. System suitability— Purity (1) Chloroform-ethanol-insoluble substances— System performance: When the procedure is run with 5 mL Warm 2.0 g of Quinidine Sulfate Hydrate with 15 mL of a of the standard solution under the above operating condi- mixture of chloroform and ethanol (99.5) (2:1) at about 509C tions, pyrrolnitrin and the internal standard are eluted in this for 10 minutes. After cooling, ˆlter through a tared glass order with the resolution between these peaks being not less ˆlter (G4) by gentle suction. Wash the residue with ˆve than 3. 10-mL portions of a mixture of chloroform and ethanol System repeatability: When the test is repeated 6 times with (99.5) (2:1), and dry at 1059C for 1 hour: the mass of the 5 mL of the standard solution under the above operating con- residue is not more than 2.0 mg. ditions, the relative standard deviation of the ratios of the (2) Related substances—Dissolve 20 mg of Quinidine peak area of pyrrolnitrin to that of the internal standard is SulfateHydrateinthemobilephasetomakeexactly100mL, not more than 1.0z. and use this solution as the sample solution. Separately, dis- Containers and storage Containers—Tight containers. solve 25 mg of cinchonine in the mobile phase to make exact- Storage—Light-resistant. ly 100 mL. Pipet 2 mL of this solution, add the mobile phase to make exactly 100 mL, and use this solution as the standard solution. Perform the test with exactly 50 mLeachofthesam- Quinidine Sulfate Hydrate ple solution and standard solution as directed under Liquid Chromatography <2.01> according to the following condi- キニジン硫酸塩水和物 tions. Determine each peak area of the sample solution by the automatic integration method, and calculate their amount by the area percentage method: the amount of dihydroquinidine sulfate is not more than 15.0z, and those of quinine sulfate and dihydroquinine sulfate are not more than 1.0z.The total area of the peaks other than the principal peak and the above peaks is not larger than the peak area of cinchonine from the standard solution. Operating conditions— Detector: An ultraviolet absorption photometer (wavelength: 235 nm). (C20H24N2O2)2.H2SO4.2H2O: 782.94 Column: A column about 4 mm in inside diameter and (9S)-6?-Methoxycinchonan-9-ol hemisulfate about 25 cm in length, packed with octadecylsilanized silica monohydrate [6591-63-5] gel (10 mm in particle diameter). Temperature: Room temperature. Quinidine Sulfate Hydrate, when dried, contains not Mobile phase: A mixture of water, acetonitrile, methane- JP XV O‹cial Monographs / Quinine Ethyl Carbonate 1051 sulfonic acid TS and a solution of diethylamine (1 in 10) It is very soluble in methanol, freely soluble in ethanol (95) (43:5:1:1). and in ethanol (99.5), soluble in diethyl ether, and practically Flow rate: Adjust the ‰ow rate so that the retention time of insoluble in water. quinidine is about 10 minutes. It dissolves in dilute hydrochloric acid. Selection of column: Dissolve 0.01 g each of Quinidine Sul- Identiˆcation (1) Determine the absorption spectrum of a fate Hydrate and quinine sulfate in 5 mL of methanol, and solution of Quinine Ethyl Carbonate in methanol (1 in add the mobile phase to make 50 mL. Proceed with 50 mLof 20,000) as directed under Ultraviolet-visible Spectrophoto- this solution under the above operating conditions, and cal- metry <2.24>, and compare the spectrum with the Reference culate the resolution. Use a column giving elution of quini- Spectrum: both spectra exhibit similar intensities of absorp- dine, quinine, dihydroquinidine and dihydroquinine in this tion at the same wavelengths. order with a resolution between quinidine and quinine and (2) Determine the infrared absorption spectrum of Qui- that between quinine and dihydroquinidine being not less nine Ethyl Carbonate as directed in the potassium bromide than 1.2, respectively. disk method under Infrared Spectrophotometry <2.25>,and Detection sensitivity: Adjust the detection sensitivity so compare the spectrum with the Reference Spectrum: both that the peak height of cinchonine obtained from 50 mLof spectra exhibit similar intensities of absorption at the same the standard solution is between 5 mm and 10 mm. wave numbers. Time span of measurement: About twice as long as the 20 retention time of quinidine beginning after the solvent peak. Optical rotation <2.49> [a]D : －42.2 – －44.09(0.5 g, calcu- (3) Readily carbonizable substances <1.15>—Take 0.20 g lated on the dehydrated basis, methanol, 50 mL, 100 mm). of Quinidine Sulfate Hydrate and perform the test: the solu- Melting point <2.60> 91–959C tion has no more color than Matching ‰uid M. Purity (1) Chloride <1.03>—Dissolve 0.30 g of Quinine Loss on drying <2.41> Not more than 5.0z (1 g, 130 9C, Ethyl Carbonate in 10 mL of dilute nitric acid and 20 mL of 3 hours). water. To 5 mL of the solution add 2 to 3 drops of silver ni- Residue on ignition <2.44> Not more than 0.1z (1 g). trate TS: no color develops. (2) Sulfate <1.14>—Dissolve 1.0 g of Quinine Ethyl Car- Assay Weigh accurately about 0.5 g of Quinidine Sulfate bonate in 5 mL of dilute hydrochloric acid and water to make Hydrate, previously dried, dissolve in 20 mL of acetic acid 50 mL, and perform the test using this solution as the test so- (100), and add 80 mL of acetic anhydride, and titrate <2.50> lution. Prepare the control solution with 1.0 mL of 0.005 mol with 0.1 molWL perchloric acid VS until the color of the solu- WL sulfuric acid VS, 5 mL of dilute hydrochloric acid and tion changes from purple through blue to blue-green (indica- water to make 50 mL (not more than 0.048z). tor: 3 drops of crystal violet TS). Perform a blank determina- (3) Heavy metals <1.07>—Proceed with 2.0 g of Quinine tion, and make any necessary correction. Ethyl Carbonate according to Method 2, and perform the Each mL of 0.1 molWL perchloric acid VS test. Prepare the control solution with 2.0 mL of Standard ＝24.90 mg of (C20H24N2O2)2.H2SO4 Lead Solution (not more than 10 ppm). (4) Related substances—Dissolve 20 mg of Quinine Ethyl Containers and storage Containers—Well-closed contain- Carbonate in the mobile phase to make exactly 100 mL, and ers. use this solution as the sample solution. Separately, dissolve Storage—Light-resistant. 25 mg of quinine sulfate in the mobile phase to make exactly 100 mL. Pipet 2 mL of this solution, add mobile phase to make exactly 100 mL, and use this solution as the standard Quinine Ethyl Carbonate solution.
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