JP XIV Dihydrocodeine Phosphate yomise kasd > oY she. ne-d Yoh fon CygNqgNO3.HyPO, 399.38 (GR,65)-4,5-Epoxy-3-methoxy-17-methylmorphinan-6-01 monophosphate [24204-13-5] Dihydrocodeine Phosphate contains not less than 98.0% of CigHzsNOs.HsPO,, calculated on the dried basis. Description Dihydrocodeine Phosphate occurs as a white to yellowish white, crystalline powder. It is freely soluble in water and in acetic acid (100), slight- ly soluble in ethanol (95), and practically insoluble in diethyl ther. ‘The pH of a solution of Dihydrocodeine Phosphate (1 in 10) is between 3.0 and 5.0. It is affected by light Identification (1) Determine the absorption spectrum of 4 solution of Dihydrocodeine Phosphate (1 in 10,000) as directed under the Ultraviolet-vsible Spectrophotometry, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wavelengths. @) Determine the infrared spectrum of Dihydrocodeine Phosphate, previously dried, as directed in the potassium ‘bromide disk method under the Infrared Spectrophotomet- zy, and compare the spectrum with the Reference Speetrum: both spectra exhibit similar intensities of absorption at the same wave numbers. @) A solution of Dihydrocodeine Phosphate (1 in 20) responds to the Qualitative Test (1) for phosphate. Purity (1) Chloride—Perform the test with 0.5 g of Di- hydrocodeine Phosphate. Prepare the control solution with 0.30 mL of 0.01 mol/L hydrochloric acid (not more than 0.02196). @) Sulfate—Perform the test with 0.20¢ of Di- hydrocodeine Phosphate. Prepare the control solution with 1.0mL of 0.005 mol/L sulfuric acid (not more than 0.240%). () Related substances—Dissolve 0.202 of Dihydro- codeine Phosphate in 10 mL of diluted ethanol (95) (1 in 2), and use this solution as the sample solution. Pipet 1 mL of the sample solution, add diluted ethanol (95) (1 in 2) to ‘make exactly SO mL, and use this solution as the standard so- lution. Perform the test with these solutions as directed un- der the Thin-layer Chromatography. Spot 10 11 of the sam- ple solution and the standard solution on a plate of silica gel with fluorescent indicator for thin-chromatography. De- ‘velop the plate with a mixture of ethanol (99.5), toluene, ace- tone and ammonia solution (28) (14:14:7:1) to a distance of about 15 om, and air-dry the plate. Examine under ultravio- let light (main wavelength: 254 nm): the spots other than the Official Monographs for Part I | 1% Dihydrocodeine Phosphate Powder 417 principal spot from the sample solution are not more intense than the spot from the standard solution. Loss on drying Not more than 1.0% (0.58, 105°C, 4 hours). Assay Weigh accurately about 0.5 g of Dil Phosphate, dissolve in 70 mL. of acetic acid (100), and ti- trate with 0.1 mol/L perchloric acid VS until the color of the solution changes from purple through blue to greenish blue (indicator: 3 drops of crystal violet TS). Perform a blank determination, and make any necessary correction. Each mL of 0.1 mol/L perchloric acid VS 9.938 mg of CygHz3NOp.HsPO, Containers and storage | Containers—Tight containers. ‘Storage—Light-resistant 1ydrovodeine 1% Dihydrocodeine Phosphate Powder te FAFA SM I% 1% Dihydrocodeine Phosphate Powder contains not less than 0.90% and not more than 1.10% of di- hydrocodeine phosphate (CisHzNO3.HyPOx: 399.38). ‘Method of preparation Dihydrocodeine Phosphate 1008 Lactose a sufficient quantity To make — 100g Prepare as directed under Powders, with the above in- sredients Identification Determine the absorption spectrum of a so- lution of 196 Dihydrocodeine Phosphate Powder (I in 100) as directed under the Ultraviolet-visible Spectrophotometry: it exhibits a maximum between 281 nm and 285 nm. ‘Assay Weigh accurately about 5g of 1% Dihydrocodeine Phosphate Powder, dissolve in water to make exactly 100 ‘mL, then pipet 10 mL. of ths solution, add exactly 10 ml. of the internal standard solution, and use this solution as the sample solution. Separately, weigh accurately about 0.05 ¢ of ditydrocodeine phosphate for assay, separately deter ined its loss on drying (105°C, 4 hours), dissolve in water to make exactly 100 mL, thea pipet 10m of this solution, add exactly 10 mL of the internal standard solution, and use {his solution asthe standard solution. Perform the test with 204L each ofthe sample solution and the standard solution as directed under the Liquid Chromatography according to the following conditions, and calculate the ratios, Or and Qs, ofthe peak area of dinydrocodeine to that ofthe intr- nal standard, Amount (mg) of dihydrocodeine phosphate (CisHasNOs.HsPO0) amount (mg) of dihydrocodeine phosphate for assay, calculated on the dried basis «Or Os418 10% Internal standard solution—A solution of ethylefucin hydrochloride (3 in 10,000), Operating conditions— Detector: An ultraviolet (wavelength: 280 nm). ‘Column: A stainless steel column about 4 mm in inside di- ameter and 15 to 25m in length, packed with octadecyl- silanized silica gel for liquid chromatography (about Sam in particle diameter). Column temperature: A constant temperature of about 40°C. Mobile phase: Dissolve 1.0 g of sodium lauryl sulfate in 500 mL. of diluted phosphoric acid (I in 1000), and adjust the pH to 3.0 with sodium hydroxide TS. To 240 mL of this solution add 70 mL of tetrahydrofuran. Flow rate: Adjust the flow rate so that the retention time of dihydrocodeine is about 9 minutes. Selection of column: Proceed with 20 uL of the standard solution under the above operating conditions, and calcu- late the resolution. Use a column giving elution of hydrocodeine and the internal standard in this order with the resolution between these peaks being not less than 4. absorption photometer Containers and storage Containers—Tight containers. 10% Dihydrocodeine Phosphate Powder YR RAZA DB 10% 10% Dihydrocodeine Phosphate Powder contains not less than 9.3% and not more than 10.7% of di- hydrocodeine phosphate (CysHz:NO:.H,PO;: 399.38). ‘Method of preparation Dilbydrocodeine Phosphate 1008 Lactose a sufficient quantity To make 1000¢ Prepare as directed under Powders, with the above in- sredients. dentification Determine the absorption spectrum of a so- lution of 10% Dihydrocodeine Phosphate Powder (I in 1000) as directed under the Ultraviolet-vsible Spectrophoto- metry: it exhibits a maximum between 281 nm and 285 nm. Assay Weigh accurately about 252 of 10% Di- hydrocodeine Phosphate Powder , dissolve in water to make exactly 100 mL, then pipet 2 mL of this solution, add exact- ly 10mL of the internal standard solution and water to make 20 mL, and use this solution as the sample solution. Separately, weigh accurately about 0.052 of di- hydrocodeine phosphate for assay, separately determined its Toss on drying (105°C, 4 hours), dissolve in water to make ex- actly 100 mL, then pipet 10 mL of this solution, add exactly 10 mL of the internal standard solution, and use this solu- tion as the standard solution. Perform the test with 20 1. cach of the sample solution and the standard solution as directed under the Liquid Chromatography according to the following conditions, and calculate the ratios, Or and Qs, of the peak area of dihydrocodeine to that of the internal standard. ihydrocodeine Phosphate Powder / Official Monographs for Part I JP XIV Amount (mg) of dihydrocodeine phosphate (CigHzNO3.H;PO,) = dihydrocodeine phosphate for assay, calculated on the dried basis x Otx5 Internal standard solution—A solution of ethylefrine hydrochloride (3 in 10,000). Operating conditions— Detector: An ultraviolet (wavelength: 280.0), Column: A stainless steel column about 4 mm in inside di- ameter and 15 to 25 cm in length, packed with octadecy silanized silica gel for liquid chromatography (5 am in parti- cle diameter). Column temperature: A constant temperature of about 40°C. Mobile phase: Dissolve 1.0 g of sodium lauryl sulfate in 500 mL of diluted phosphoric acid (1 in 1000), and adjust the pH to 3.0 with sodium hydroxide TS. To 240 mL of this solution add 70 mL. of tetrahydrofuran. Flow rate: Adjust the flow rate so that the retention time of dihydrocodeine is about 9 minutes. Selection of column: Proceed with 20 uL of the standard solution under the above operating conditions, and calcu- late the resolution. Use a column giving elution of di- hydrocodeine and the internal standard in this order with the resolution between these peaks being not less than 4. absorption photometer Containers and storage | Containers—Tight containers. Dihydroergotamine Mesilate PIR KER Sy et mf CigFEs:NsOs.CH,O,S: 679.78 G'S 10R}-5'-Benzy/-9,10-dinydro-12’-hydroxy.2°- methylergotaman-3’,6’,18-rione monomethanesulfonate (6190-39-2) Dihydroergotamine Mesilate contains not less than 97.0% of CgHsyNsOs-CH,O,S, calculated on the dried basis. Description Dihydroergotamine Mesitate occurs as a white to yellowish white or grayish white to reddish white powder. Is freely soluble in acetic acid (100), sparingly soluble ‘methanol and in chloroform, slightly soluble in water and ethanol (95), and practically insoluble in acetic anhydride and in diethylether. It is gradually colored by light. Melting point: about 214°C (with decomposi