2ROO5S5 CLORHIDRATO DE RANITIDINA RANITIDINE HYDROCHLORIDE VER GRAFICO G-740 [13] H[22]N(4]O[3]S.HC1 350,87 1,1-Ethenediamine, N-(2-[{[5-[ (dimethylamino)methyl]-2- furanyl}methyl] tio] ethyl}-N'-methyl-2-nitro- ;monohydrochloride. N- (2-[[ [5~[ (Dimethylamino) methy1]-2- furanyl)methyl] tio] ethyl ]-N'-methy1- 2-nitro-1,1-ethenediamine, hydrochloride [66357-59-3]. >> El Clorhidrato de Ranitidina contiene no menos de 97,5 por ciento y no ms de 102,0 por ciento de C[13]H[22]N[4]0[3]S.HC1, calculado sobre la sustancia seca. ENVASE Y ALMACENAMIENTO - Conservar en envases de cierre perfecto, resistentes a la luz. SUSTANCIAS DE REFERENCIA USP - Clorhidrato de Ranitidina SR-USP. Ranitidina, Compuesto Relacionado A SR-USP. Ranitidina, Compuesto Relacionado B SR-USP. Ranitidina, Compuesto Relacionado C SR-USP. IDENTIFICACION ~ A: Absorcién Infrarroja <197M>. Absorcién Ultravioleta <197U> - Solucién: 10 pg por mL. Medio: agua. Las absortividades a 229 nm y 315 nm, calculadas sobre la sustancia seca, no difieren en ms de 3,08. C: Una solucién de Clorhidrato de Ranitidina responde a las pruebas para Cloruro <191>, PH <791>: entre 4,5 y 6,0, en una solucién (1 en 100). PERDIDA POR SECADO <731> - Secar al vacio a 60° durante 3 horas: no pierde ms de 0,75% de su peso. RESIDUO DE IGNICION <281>: no ms de 0,18. PUREZA CROMATOGRAFICA - Solucién de Prueba - Preparar una solucién en metanol que contenga 22,3 mg de Clorhidrato de Ranitidina por mb. Soluciones Est ndar - Disolver una cantidad exactamente pesada de Clorhidrato de Ranitidina SR-USP en metanol y diluir con metanol hasta obtener una Solucién Est ndar A con una concentracién conocida de aproximadamente 0,22 mg por mL. Diluir cuantitativamente porciones de Solucién Est ndar A con metanol hasta obtener Soluciones Est ndar B, C y D, con concentraciones de 110; 66 y 11 pg por mb, respectivamente. Solucién de Resolucién ~ Disolver una cantidad exactamente pesada de Ranitidina, Compuesto Relacionado A SR-USP en metanol hasta obtener una solucién con una concentracion conocida de aproximadamente 1,27 mg por mL.Preparacién de Identificacién - Disolver una cantidad exactamente pesada de Ranitidina, Compuesto Relacionado B SR-USP en metanol hasta obtener una solucién con una concentracién conocida de aproximadamente 1 mg por mL. Procedimiento - Aplicar por separado 10 pL de las Soluciones de Prueba, las Soluciones Est ndar y la Solucién de Identificacién sobre una placa para cromatografia en capa delgada (ver Cromatografia <621>), recubierta con mezcla de gel de silice para cromatografia de 0,25 mm de espesor. Aplicar por separado 10 pL adicionales de la Solucién de Prueba sobre la misma placa y, sobre la mancha producida, aplicar 10 pL de la Solucién de Resolucién. Dejar secar las manchas y desarrollar los cromatogramas en un sistema de solventes que consista en una mezcla de acetato de etilo, alcohol isopropilico, hidréxido de amonio y agua (25:15:5:1) hasta que el frente del solvente haya recorrido no menos de 15 cm desde el origen. Retirar la placa de la c mara de desarrollo, marcar el frente del solvente y dejar secar al aire. Exponer la placa a vapores de yodo en una c mara cerrada hasta que el cromatograma se revele completamente. Examinar la placa comparar las intensidades de odalquisr anche becundazia observada en el cromatograma de la Solucién de Prueba con las intensidades de las manchas principales obtenidas en los cromatogramas de las Soluciones Est ndar A, B, C y D la Solucién de Identificacién: se cumplen los requisitos de aptitud del sistema si se produce una resolucién completa entre las manchas primarias en el cromatograma de la Solucién de Prueba y la Solucién de Resolucién combinadas y si se observa una mancha en el cromatograma de la Solucién Est ndar D. Ninguna mancha observada en el cromatograma de la Solucién de Prueba, al valor de R[f] correspondiente al de la mancha principal producida por la Solucién de Identificacién, es mayor en tamafio o intensidad que la mancha principal obtenida a partir de la Solucién Est ndar B la cual corresponde a no mos de 0,5% y ninguna otra mancha en el cromatograma de la Solucién de Prueba excede el tamafio y la intensidad de la mancha principal obtenida a partir de la Solucién Est ndar C (0,3%). La suma de las intensidades de todas las manchas secundarias obtenidas a partir de la Solucién de Prueba corresponde a no ms de 1,08. IMPUREZAS ORGANICAS VOLATILES, Método I <467>: cumple con los requisitos. VALORACION - (NOTA - Donde se indican las respuestas de los picos, emplear las reas de los picos]. Fase Movil - Preparar una mezcla filtrada y desgasificada de metanol y acetato de amonio acuoso 0,1 M (85:15). Hacer roa.JP XVI ditions, and determine each peak area by the automatic tegration method: the atea of the peak having the relative retention time of about 0.7 to rabeprazole from the sample solution is not larger then 4/5 times the peak area of Fabeprazole from the standard solution, the area ofthe pale other than rabeprazole and ather than the peak mentioned above From the sample solution isnot larger than 1/10 times the peak area of rabeprazoe from the standard solution, and the total area of the peaks other than rabeprazole from the ‘sample solution isnot larger than the peak area of rabeprs- ale from the standard solution, Operating conditions — Detector, column, column temperature, mobile pase, and flow rate: Proceed as directed in the operating conditions in the Assay. Time span of measurement: About 3 times as long asthe retention time of rabeprazole, beginning after the solvent, peak. System suitability — Test for required detectability: Pipet § mL. ofthe standard solution, and add a mixture of methano and 0.01 mol/L so dium hydroxide TS (3:2) to make exactly 100 mL. Confirm that the peak area of rabeprazole obtained with 10 ofthis Solution is equivalent to 3.5 to 65% of that with IOuL of the standard solution, System performance: When the procedure it un with 10 UL of the standard solution under the above operating con- ditions, the mumber of theoretical plates and the symmetry factor ofthe peak of rabeprazole are not less than 3000 and not mare than 1.5, respectively ‘System repestabiliy: When the tet is repeated 6 times with 10 aL ofthe standard solution under the above operat- ing conditions, the relative standard deviation of the peal tea of rabeprazole is not more than 2.0%. @) Residual solvent—Being specified separately Loss on drying <2.42 Not more than 1.0% (Ug, in vac ums, phosphors (V) oxide, 24 hours. Take the sample while ‘avoiding moisture absorption). Assay Take the sample tobe tested while voiding moisture absorption. Weigh accurately about 0.1g each of Rabepra zole Sodium and Rabeprazole Sodium RS (separately deter- mine the loss on drying @2.42> under the same conditions as Rabeprazole Sodium), dissolve each in a mixture of metha- nol and 0.01 mol/L sodium hydroxide TS (3:2) to make ex- ‘actly 25 mL. Pipet SL each of thetesoltions, add exactly 10m of the internal standard solution to each, then add a mixture of methanol and 0.01 mol/L sodium hydeoxide TS. (622) to make 100 mL, and use these solutions as the sample solution and the standard solution, respectively. Perform the {est with 10 i. each of the sample solution end standard so- Iution a directed under Liquid Chromatography <2.01> ac- cording to the following conditions, and calculate the ratios, r and Qs, of the peak area of rabeprazole to that of the internal standard ‘Amount (mg) of sodium rabeprazole (CisHsNNaO,S) = Ms % Qr/Qs ‘Mg: Amount (mg) of Rabeprazole Sodium RS, calculated ‘onthe deed basis Interna standard solurion—A solution of -amino-2-methyl- naphthalene in a mixture of methanol and 0.01 mol/L s0- Official Monographs / Ranitidine Hydrochloride 1333 dium hydroxide TS (3:2) (1 in 250). Operating conditions— Detector: An ultraviolet absorption photometer (waver length: 290 nm). ‘Column: stainless steel column 4.6 mm in inside diame ter and 15 em in length, packed with octadeeysilanizedslica te for liquid chromatography (5 um in particle diameter). ‘Column temperature: A constant temperature of about 30°C. ‘Mobile phase: A mixture of methanol and 0.05 mol/L. phosphate buffer solution, pH 7.0 (3:2). Flow rate: Adjust the flow rate so thatthe retention time of rabeprazoe is about $ minutes, System sutability System performance: When the procedure Is run with 10 {ML of the standard solution under the above operating con- ditions, rabeprazole and the internal standard are eluted in this order with the resolution between these peaks being not less than 4, and the symmetry factor ofthe peak of rabepra- zle is not more than 2. System repeatability: When the testis repeated 6 times with 10 11 ofthe standard solution under the above operat: ing conditions, the elative standard deviation of the ratio of the peak area of rabeprazole to that of the internal sandard Is not more than 1.0% Containers and storage Containers—Tight containers. Freeze-dried Inactivated Tissue Culture Rabies Vaccine HORNER SEER 7 FD Freeze-dried Inactivated Tissue Culture Rabies Vac- cine is a dried preparation containing inactivated ra- bies virus. It conforms to the requirements of Freeze-dried In- activated Tissue Culture Rabies Vaccine in the Mini- ‘mum Requirements of Biologic Products. Description Freeze-dred Inactivated Tissue Culture Rabies Vacvine becomes a colorless or ight yellow-red clea liquid on addition of solvent. Ranitidine Hydrochloride sary rie CyHaNO,S.HCt: 350.86 (162).N-2-((5-(Dimethylamino)methy}furan- 2 yimethyDsulfanylfethy!)-N'-methy-2-nitroethene- 1,1-diamine monohydrochioride (65387-59.3 Ranitidine Hydrochloride, when dried, contains not less than 97.5% and not more than 102.0% of1334 CylinN.0,8.HC1. Description Ranitidine Hydrochloride occurs as @ white 10 pale yellow, erstalline or fine granular powder. tis very soluble in water, frely soluble in methanol, and slightly soluble in ethanol (9.9) Tes hygroscopic. It's gradually colored by Hight. ‘Melting point: about 140°C (with decomposition. entitication (1) Determine the absorption spectrum of a solution of Ranitidine Hydrochloride (1 in 100,000) as directed under Ulravilet-vsible Spectrophotometry 220, ‘and compare the spectrum withthe Reference Spectrum of the spectrum of a solution of Ranitidine Hydrochloride RS prepared in the same manner asthe sample solucon: both spectra exhibit similar Intensities of absorption at the same wavelength. {@) Determine the infrared absorption spectrum of Ranitidine Hydrochloride as directed in the paste method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spectrum or the spectrum of previously dried Ranitidine Hydrochloride RS: both spectra exhibit similar intensities of absorption at the same wave numbers {@) A solution of Ranitidine Hydrochloride (1 in 50) responds tothe Qualitative Tests <.09> fer chloride. pH «2.50 The pH of 2 solution obtained by dissolving 10g of Ranitidine Hydrochloride in 100 mL of water is between 4.5 and 6.0. Party (2). Clarity and color of solution—A solution of Ranitidine Hydrochloride (1 in 10)is clear and pale yellow to light yellow, {@) Heavy metals <1.07>—Proceed with 2.0 of Raniti- dine Hydrochloride according to Method 2, and perform the test, Prepare the control solution with 2.0 mL of Standard ‘Lead Solution (not mere than 10 ppm). 1@)_Areeic <1.1P>—Prepare the tet solution with 1.05 ‘of Ranitidine Hydrochloride according to Method 4, and perform the test (not more than 2 ppm) (@)_ Related substances Conduct this procedure without ‘exposure fo light, using light-resistant vessels. Dissolve (0.22 of Ranitidine Hydrochloride in methanol to make ex actly 10 mL, and use this solution as the sample solution. Pipet 0.5 ml. of the sample solution, add methanol to make exactly 100 mL, and use this solution asthe standard solu- tion (1), Pipet 6m, 4mL, 2mL and I mL of the standard solution (1), add to each methanol to make exactly 10 mL, and use these solutions as the standard solution (2), the standard solution (3), the standard solution (4) and the standard solution (5), respectively. Separately, dissolve 12.7 img of rantidinediamine in methanol to make exactly 10 L, ‘and use this solution as the standard solution (6). Perform the test with these solutions as directed under Thinayer Chromatography <2.03>. Spot 10 ul each ofthe sample solt- tion and standard solutions (1), 2), @), (4) and (5) on a plate of silica gel for thin-layer chromatography. Separately, spot 10s ofthe sample solution on the plate, then spot 10 1 of the standard solution (6) on the spotted position ofthe sam- pl solution. Immediately develop the plate with a mixture of ‘ethyl acetate, -propanol, ammonia solution (28) and water {QSuS:S:1) to a disance of about 15cm, and air-dry the plate. Allow the plate to standin iodine vapor until the spat Ranitidine Hydrochloride / Official Monographs IP XVI ‘rom the standard solution (6) appears: the spot obtained from the standard solution (6) is completely separated from the principal spot from the sample solution. The spot having RE value of about 0.7 from the sample solution is not more intense than the spot from the standard solution (1), the spots other than the principal spot andthe spot of RE value ‘of about 0.7 from the sample solution are not mote intense than the spot from the standard solution @), and the total mount of these related substances, calculated by compati- son with the spots from the standard solutions (1), 2), @)y (@) and (5), is not more than 1.0%. Loss on drying 2. Not more than 0.7556 (1, In vacu- vm, 60°C, 3 hours). [Residue on ignition <2.40 Not mote than 0.1% (1g). Assay Weigh accurately about 20 mg of Ranitidine Hydro- chloride and Ranitidine Hydrochloride RS, previously dried, fisoive each inthe mobile phase to make exactly 200 mL, ‘and use these solutions asthe sample solution and standard solution. Perform the test with exactly 10,L each of the ample solution and standard solution as directed under Liquid Chromatography <2.01> according to the following conditions, and determine the peak ateas, Ar and Ay, of ranitidine, Amount (mg) of CyHzN,O,S.HCI = Me x Av/As ‘Mg: Amount (mg) of Ranitidine Hydrochloride RS Operating conditions — Detector: An ultraviolet absorption photometer (wave- length: 322 nm). ‘Column: A stainless steel column 4.6 mm in inside diame- ter and 20em in lengths, packed with octadecylslanized silica te for liquid chromatography (10m in particle diameter). ‘Column temperature: A constant temperature of about asec. ‘Mobile phase: A mixture of methanol and diluted 0.5 ‘mol/L ammonium acetate TS (I in $) (173) Flow rate: Adjust the flow rate so thatthe retention time of ranitidine is about $ minutes. System suitabiliy— ‘System performance: Dissolve 20 mg of Ranitidine Hydro chloride and $ mg of benzalphthalide in 200 mL of the mo- bile phase. When the procedure is run with 10 L of this s0- Iution under the above operating conditions, benzalphthalide and ranitidine are eluted in this order withthe resoltion be- ‘een these peaks being not lxs than 2.0. ‘System repeatability: When the testis repeated 6 times with 10 aL of the standard solution under the above operat- ing condition, the relative standard deviation of the peak area of ranitidine is not more than 1.0%. Containers and storage Containers—Tight containers. Storage—Light-esstant,