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【答案】应助回帖
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感谢参与，应助指数 +1
痴夷子皮: 金币+1, 谢谢交流，这个是35版的，呵呵。 2012-09-11 17:04:15
Carvedilol Tablets
DEFINITION
Carvedilol Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of carvedilol (C24H26N2O4).
IDENTIFICATION
• A. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.
• B. Ultraviolet Absorption 197U
Wavelength range: 250–400 nm
Cell: 0.2 cm
Sample solution: 0.125 mg/mL of carvedilol prepared as follows. Place 10 Tablets in a 150-mL polypropylene tube, and disintegrate the Tablets in methanol (100 mL for the Tablet strengths 3.125, 6.25, and 25 mg, and 50 mL for the Tablet strength 12.5 mg) using a mechanical homogenizer. Transfer the homogenate to an appropriate volumetric flask, and dilute with methanol to volume. Pass through a suitable PTFE filter of 0.45-µm pore size.
ASSAY
• Procedure
Buffer: Dissolve 0.7 g of anhydrous monobasic potassium phosphate in 500 mL of water, and add 10 mL of triethylamine. Adjust with phosphoric acid to a pH of 3.0 ± 0.1.
Mobile phase: Dissolve 1.04 g of sodium dodecyl sulfate in 150 mL of Buffer in a 2-L volumetric flask, and sonicate. Add 720 mL of acetonitrile, and dilute with water to volume. Pass through a nylon 66 filter of 0.2-µm pore size.
Diluent: Methanol and 1 M hydrochloric acid (9:1)
Methanol solution: Methanol and water (1:1)
Standard solution: 0.0125 mg/mL of USP Carvedilol RS prepared as follows. Dissolve a quantity of USP Carvedilol RS in a mixture of Diluent and water (9:1), and sonicate until the solution is clear. Dilute with Methanol solution to obtain the required final concentration.
Sample stock solution: Transfer a portion of the powdered Tablets (NLT 20), equivalent to 25 mg of carvedilol, to a 100-mL volumetric flask. Add 10 mL of water, shake by hand, then add 70 mL of Diluent, and sonicate for 30 min. Shake on a mechanical shaker for about 30 min, and dilute with Diluent to volume to prepare a 0.25-mg/mL solution. Centrifuge an appropriate amount (about 50 mL) at 2000 rpm for 10 min.
Sample solution: 0.0125 mg/mL of carvedilol in Methanol solution from the Sample stock solution. Pass a portion of the solution through a suitable syringe filter of 0.45-µm pore size, discard the first 5 mL, and use the filtrate as the Sample solution.
Chromatographic system
(See Chromatography 621, System Suitability.)
Mode: LC
Detector: UV 240 nm
Column: 4.6-mm × 50-mm; packing L7
Column temperature: 40
Flow rate: 1 mL/min
Run time: 30 min
Injection size: 25 µL
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 the labeled amount of carvedilol (C24H26N2O4) in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × 100
rU = = peak response from the Sample solution
rS = = peak response from the Standard solution
CS = = concentration of the Standard solution (mg/mL)
CU = = nominal concentration of the Sample solution (mg/mL)
Acceptance criteria: 90.0%–110.0%
PERFORMANCE TESTS
• Dissolution 711
Test 1
Medium: 0.7% (7 mL/L) of hydrochloric acid, adjusted with 50% (w/w) sodium hydroxide to a pH of 1.45 ± 0.2; 900 mL; deaerated
Apparatus 2: 50 rpm
Time: 30 min
Standard stock solution: Transfer about 7 mg of USP Carvedilol RS to a 250-mL volumetric flask. Add 5 mL of methanol, and sonicate until dissolved. Cool to room temperature, dilute with Medium to volume, and mix well.
Standard solution: On the basis of the label claim and using the Standard stock solution, prepare a solution of USP Carvedilol RS in Medium having an appropriate concentration (CS), as shown in Table 1.
Table 1
Label Claim
(mg) CS (mg/mL)
25 0.028
12.5 0.014
6.25 0.007
3.125 0.0035
Sample solution: Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size.
Analytical wavelengths: 285 and 380 nm
Path length: 1 cm
Blank: Medium
Analysis: Calculate the corrected absorbance of the Standard solution and the Sample solution:
Acorr = A285 A380
Acorr = = corrected absorbance of the Standard solution or the Sample solution
A285 = = absorbance of the Standard solution or the Sample solution at 285 nm
A380 = = absorbance of the Standard solution at 380 nm
Calculate the percentage of carvedilol dissolved:
Result = (AU/AS) × CS × (V/L) × 100
AU = = corrected absorbance from the Sample solution
AS = = corrected absorbance from the Standard solution
CS = = corrected concentration of the Standard solution (mg/mL)
V = = volume of Medium, 900 mL
L = = label claim (mg/Tablet)
Tolerances: NLT 80% (Q) of the labeled amount of carvedilol (C24H26N2O4) is dissolved.
Test 2: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 2.
Medium: Simulated gastric fluid without enzymes; 900 mL
Apparatus 2, Time, Standard stock solution, Standard solution, Sample solution, and Analysis: Proceed as directed in Test 1.
Tolerances: NLT 80% (Q) of the labeled amount of carvedilol (C24H26N2O4) is dissolved.
Test 3: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 3.
Medium: Simulated gastric fluid with pepsin, pH 1.45 (dissolve 12.0 g of sodium chloride and 19.2 g of purified pepsin (porcine origin, activity 800–2500 Units/mg of protein) in 18 mL of hydrochloric acid and sufficient water to make 6 L; adjust with hydrochloric acid to a pH of 1.45); 900 mL
Apparatus 2: 50 rpm
Time: 30 min
Buffer: 2.72 g/L of monobasic potassium phosphate in water. Adjust with phosphoric acid to a pH of 2.0 ± 0.05.
Mobile phase: Buffer and acetonitrile (650:350)
Standard stock solution: 1.4 mg/mL of USP Carvedilol RS in methanol
Standard solution: Dilute the Standard stock solution with Medium to obtain a final concentration of (L/900) mg/mL, where L is the Tablet label claim, in mg.
Sample solution: Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size.
Chromatographic system
(See Chromatography 621, System Suitability.)
Mode: LC
Detector: UV 240 nm
Column: 4.6-mm × 15-mm; 5-µm packing L7
Column temperature: 35
Flow rate: 1.5 mL/min
Injection size: 20 µL
System suitability
Sample: Standard solution
Suitability requirements
Column efficiency: NLT 3500 theoretical plates
Tailing factor: NMT 2.0
Relative standard deviation: NMT 2.0%
Analysis: Calculate the percentage of carvedilol dissolved:
Result = (rU/rS) × (CS/L) × V × 100
rU = = peak response from the Sample solution
rS = = peak response from the Standard solution
CS = = concentration of the Standard solution (mg/mL)
L = = label claim (mg/Tablet)
V = = volume of Medium, 900 mL
Tolerances: NLT 80% (Q) of the labeled amount of carvedilol (C24H26N2O4) is dissolved.
• Uniformity of Dosage Units 905
Buffer, Mobile phase, Diluent, Methanol solution, Standard solution, Chromatographic system, and System suitability: Proceed as directed in the Assay.
Sample solution: 0.25 mg/mL of carvedilol prepared as follows. Place 1 Tablet into a volumetric flask of appropriate size, based on the label claim. Add water to the flask up to about 10% of volume, and shake by hand to disintegrate the Tablet. Fill the flask up to 75% of volume with Diluent, and sonicate for 30 min to obtain complete disintegration. Shake on a mechanical shaker for 30 min, allow to cool, and dilute with Diluent to volume. Centrifuge an appropriate amount of this solution for 10 min at 2400 rpm, and transfer 4 mL of supernatant into a 100-mL volumetric flask. Fill the flask to about 85% of volume with Methanol solution, and sonicate for 20 min, with intermittent shaking. Dilute with Methanol solution to volume, and pass through a suitable syringe filter of 0.45-µm pore size.
Analysis
Samples: Standard solution and Sample solution
Calculate the percentage of carvedilol (C24H26N2O4) in the Tablet taken:
Result = (rU/rS) × (CS/CU) × 100
rU = = peak response from the Sample solution
rS = = peak response from the Standard solution
CS = = concentration of the Standard solution (mg/mL)
CU = = nominal concentration of the Sample solution (mg/mL)
Acceptance criteria: Meet the requirements
IMPURITIES
• Organic Impurities
Buffer, Mobile phase, Diluent, Methanol solution, and Sample stock solution: Prepare as directed in the Assay.
Standard stock solution: Use the Standard solution from the Assay.
Standard solution: 1.25 µg/mL USP Carvedilol RS in a mixture of Diluent and water (1:1) from the Standard stock solution
Sample solution: Dilute with water to volume, 25 mL of the supernatant from the Sample stock solution in a 50-mL volumetric flask. Pass a portion of the solution through a suitable syringe filter of 0.45-µm pore size.
Chromatographic system: Proceed as directed in the Assay, except for Injection size.
Injection size: 15 µL
System suitability
Sample: Standard solution
Suitability requirements
Tailing factor: NMT 2.0
Relative standard deviation: NMT 3.0%
Analysis
Samples: Standard solution and Sample solution
Calculate the percentage of each impurity in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × 100
rU = = peak response of each impurity from the Sample solution
rS = = peak response of carvedilol from the Standard solution
CS = = concentration of USP Carvedilol RS in the Standard solution (mg/mL)
CU = = nominal concentration of carvedilol in the Sample solution (mg/mL)
Acceptance criteria
Individual impurities: NMT 0.2% (specified or unspecified)
Total impurities: NMT 1.0%
[Note—Disregard any peaks with a relative retention time less than or equal to 0.04 and peaks with less than 0.05% of the nominal carvedilol peak response in the Sample solution. ]
ADDITIONAL REQUIREMENTS
• Packaging and Storage: Preserve in tight, light-resistant containers protected from moisture. Store at controlled room temperature.
• Labeling: When more than one Dissolution test is given, the labeling states the test used only if Test 1 is not used.
• USP Reference Standards 11
USP Carvedilol RS
Auxiliary Information— Please check for your question in the FAQs before contacting USP.
Topic/Question Contact Expert Committee
Monograph Sujatha Ramakrishna, Ph.D.
Senior Scientific Liaison
1-301-816-8349 (SM22010) Monographs - Small Molecules 2
711 Margareth R.C. Marques, Ph.D.
Senior Scientific Liaison
1-301-816-8106 (GCDF2010) General Chapters - Dosage Forms
Reference Standards RS Technical Services
1-301-816-8129
rstech@usp.org
USP35–NF30 Page 2515
Pharmacopeial Forum: Volume No. 34(3) Page 579 |
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