Tài liệu Dược điển anh 5086 5087 zonisamide

Accessed from 128.83.63.20 by nEwp0rt1 on Sun Nov 27 00:57:01 EST 2011 5086 Zolpidem / Official Monographs rS Add the following: •• LABELING: When more than one Dissolution test is given, the labeling states the Dissolution test used only if Test 1 is not used.• (RB 1-Jul-2011) • USP REFERENCE STANDARDS 〈11〉 USP Zolpidem Related Compound A RS N,N-Dimethyl-2-(7-methyl-2-p-tolylimidazo[1,2-a]pyridin-3yl)acetamide. C19H21N3O 307.39 USP Zolpidem Tartrate RS . Zonisamide C8H8N2O3S 212.23 1,2-Benzisoxazole-3-methanesulfonamide [68291-97-4]. DEFINITION Zonisamide contains NLT 98.0% and NMT 102.0% of C8H8N2O3S, calculated on the anhydrous basis. IDENTIFICATION • A. INFRARED ABSORPTION 〈197K〉 • B. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay. ASSAY • PROCEDURE Buffer: 1.36 g/L of monobasic potassium phosphate in water. Adjust the pH to 3.0 ± 0.1 with 10% phosphoric acid. Mobile phase: Acetonitrile, methanol, and Buffer (1:1:8) Standard solution: 0.1 mg/mL of USP Zonisamide RS in Mobile phase Sample solution: 0.1 mg/mL of Zonisamide in Mobile phase Chromatographic system (See Chromatography 〈621〉, System Suitability.) Mode: LC Detector: UV 240 nm Column: 4.6-mm × 25-cm; 5-µm packing L1 Flow rate: 1.5 mL/min Injection size: 20 µL System suitability Sample: Standard solution Suitability requirements Column efficiency: NLT 5000 theoretical plates Tailing: NMT 1.8 Relative standard deviation: NMT 2.0% Analysis Samples: Standard solution and Sample solution Calculate the percentage of C8H8N2O3S in the portion of Zonisamide taken: Result = (rU/rS) × (CS/CU) × 100 rU USP 35 = peak response of zonisamide from the Standard solution CS = concentration of USP Zonisamide RS in the Standard solution (mg/mL) CU = concentration of Zonisamide in the Sample solution (mg/mL) Acceptance criteria: 98.0%–102.0% on the anhydrous basis IMPURITIES Inorganic Impurities • HEAVY METALS, Method II 〈231〉: NMT 10 ppm • RESIDUE ON IGNITION 〈281〉: NMT 0.1% Organic Impurities • PROCEDURE Mobile phase: Prepare as directed in the Assay. Standard solution: 1 µg/mL of USP Zonisamide RS and 1.5 µg/mL of USP Zonisamide Related Compound A RS in Mobile phase Sample solution: 1.0 mg/mL of Zonisamide in Mobile phase Chromatographic system: Prepare as directed in the Assay. Run time: 2 times the retention time of the zonisamide peak System suitability Sample: Standard solution Suitability requirements Resolution: NLT 10.0 between zonisamide related compound A and zonisamide Relative standard deviation: NMT 10.0% for both zonisamide and zonisamide related compound A peaks Analysis Samples: Standard solution and Sample solution Calculate the percentage of zonisamide related compound A in the portion of Zonisamide taken: Result = (rU/rS) × (CS/CU) × (Mr1/Mr2) × 100 rU = peak response of zonisamide related compound A from the Sample solution rS = peak response of zonisamide related compound A from the Standard solution CS = concentration of USP Zonisamide Related Compound A RS in the Standard solution (mg/mL) CU = concentration of zonisamide related compound A in the Sample solution (mg/mL) Mr1 = molecular weight of zonisamide related compound A (free acid), 213.23 Mr2 = molecular weight of USP Zonisamide Related Compound A RS (sodium salt), 235.23 Calculate the percentage of any unspecified impurity in the portion of Zonisamide taken: Result = (rU/rS) × (CS/CU) × 100 rU rS CS CU = peak response of each impurity from the Sample solution = peak response of zonisamide from the Standard solution = concentration of USP Zonisamide RS in the Standard solution (mg/mL) = concentration of Zonisamide in the Sample solution (mg/mL) = peak response of zonisamide from the Sample solution Official from May 1, 2012 Copyright (c) 2011 The United States Pharmacopeial Convention. All rights reserved. Accessed from 128.83.63.20 by nEwp0rt1 on Sun Nov 27 00:57:01 EST 2011 USP 35 Official Monographs / Zonisamide 5087 Acceptance criteria Individual impurities: See Impurity Table 1. Total impurities: NMT 0.3% Impurity Table 1 Name Zonisamide related compound Aa Zonisamide Any unspecified individual impurity a Relative Retention Time 0.51 Acceptance Criteria, NMT (%) 0.15 1.0 — — 0.10 1,2-Benzisoxazole-3-methane sulfonic acid. SPECIFIC TESTS • WATER DETERMINATION, Method I 〈921〉: NMT 0.8% ADDITIONAL REQUIREMENTS • PACKAGING AND STORAGE: Preserve in well-closed containers, and store at room temperature. • USP REFERENCE STANDARDS 〈11〉 USP Zonisamide RS USP Zonisamide Related Compound A RS 1,2-Benzisoxazole-3-methanesulfonic acid sodium salt. C8H6NNaO4S 235.19 [CAS-73101-64-1] System suitability Sample: Standard solution Suitability requirements Tailing factor: NMT 2.0 Relative standard deviation: NMT 2.0% Analysis Samples: Standard solution and Sample solution Calculate the percentage of zonisamide (C8H8N2O3S) in the portion of Capsules taken: Result = (rU/rS) × (CS/CU) × 100 rU = peak response of zonisamide from the Sample solution rS = peak response of zonisamide from the Standard solution CS = concentration of USP Zonisamide RS in the Standard solution (mg/mL) CU = nominal concentration of zonisamide in the Sample solution (mg/mL) Acceptance criteria: 90.0%–110.0% PERFORMANCE TESTS • DISSOLUTION 〈711〉 Medium: Water; 900 mL Apparatus 2: 75 rpm, with sinkers (see Figure 1) . Zonisamide Capsules DEFINITION Zonisamide Capsules contain NLT 90.0% and NMT 110.0% of zonisamide (C8H8N2O3S), based on label claim. IDENTIFICATION • The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay. ASSAY • PROCEDURE Mobile phase: Acetonitrile, methanol, and 0.1% trifluoroacetic acid (5:4:16) Standard stock solution: 1 mg/mL of USP Zonisamide RS in methanol Standard solution: 0.1 mg/mL of zonisamide in Mobile phase, from the Standard stock solution Sample stock solution: 1 mg/mL of zonisamide in methanol from the contents of NLT 10 Capsules with Capsule shell. [NOTE—Sonicate, and shake for 15 min.] Alternately, the Sample stock solution can be prepared as follows: Place NLT 10 Capsules in a suitable volumetric flask. Fill 20% of the final volume with water. Stir, and warm slightly for 30 min. Dilute with Mobile phase to volume. Sample solution: 0.1 mg/mL of zonisamide in Mobile phase, from the Sample stock solution Chromatographic system (See Chromatography 〈621〉, System Suitability.) Mode: LC Detector: UV 237 nm Column: 4.6-mm × 25-cm; 5-µm packing L1 Column temperature: 30° Flow rate: 1.0 mL/min Injection size: 10 µL Run time: 1.5 times the retention time of the zonisamide peak Figure 1. Sinker. Time: 45 min Determine the percentage of zonisamide dissolved using one of the following procedures. Spectrophotometric procedure Standard stock solution: 0.6 mg/mL of USP Zonisamide RS in methanol Standard solution: Dilute the Standard stock solution with Medium to obtain solutions with final concentrations as given in Table 1. Table 1 Capsule Strength (mg) 25 50 100 Final Concentration (µg/mL) 13 13 22 Sample solution: 10 mL of the solution under test. Dilute the filtrate with Medium as given in Table 2. Table 2 Capsule Strength (mg) 25 50 100 Volume of Filtrate (mL) 5.0 5.0 5.0 Official from May 1, 2012 Copyright (c) 2011 The United States Pharmacopeial Convention. All rights reserved. Final Volume (mL) 10.0 25.0 25.0