Validasi Zat Aktif Amlodipine Besilate

8/10/2019 Validasi Zat Aktif Amlodipine Besilate

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Published on USP Medicines Compendium(https://mc.usp.org)

Amlodipine Besylate

Final Authorized Version 1.0

C20H25ClN2O5 C6H6O3S 567.05

3,5-Pyridinedicarboxylic acid, 2-[(2-aminoethoxy)methyl]-4-(2-chlorophenyl)-1,4-dihydro-6-methyl-, 3-ethyl 5-methyl ester, ()-,monobenzenesulfonate;

3-Ethyl 5-methyl ()-2-[(2-aminoethoxy)methyl]-4-(o-chlorophenyl)-1,4-dihydro-6-methyl-3,5-pyridinedicarboxylate,

monobenzenesulfonate [111470-99-6].

Monohydrate 585.07

Amlodipine Besylate is a light-sensitive, white to almost white powder. It is freely soluble in methanol; sparingly soluble in alcohol; and

slightly soluble in 2-propanol and in water.

Performance-Based Monograph(Contains tests, procedures, and acceptance criteria for the material under test. It also includes the criteria-based procedures to

demonstrate that anAcceptable Procedureis equivalent to the Reference Procedures.)

DEFINITION

Amlodipine Besylate contains NLT 98.0% and NMT 102.0% of amlodipine besylate (C20H25ClN2O5 C6H6O3S), calculated on the anhydrous

basis.

IDENTIFICATION

A. INFRAREDABSORPTION

B. OPTICAL

ROTATION

Sample solution:10 mg/mL in methanol

Acceptance criteria:-0.10 to +0.10, measured at 20

ASSAY

PROCEDURE

Standard solution: USP Amlodipine Besylate CRM in an appropriate diluent

Sample solution: Amlodipine Besylate in an appropriate diluent

Analytical system: Use a procedure validated as described in MCgeneral chapterAssessingValidation Parameters for Reference

and Acceptable Procedures .

System performance requirements

Precision:Meets the requirements for 98%102.0%

Accuracy:Meets the requirements for 98.0%102.0%

Specificity:Meets the requirements

Range:Meets the requirements
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Analysis

Samples:Standard solution andSample solution

Calculate the percentage of amlodipine besylate (C20H25ClN2O5 C6H6O3S) in the Sample solution:

Result = (rU/rS) (CS/CU) 100

rU = response from the Sample solution

rS = response from the Standard solutionCS = concentration of the Standard solution

CU = concentration of the Sample solution

Acceptance criteria:98.0%102.0% on the anhydrous basis

IMPURITIES

RESIDUEONIGNITION: NMT 0.1%

ELEMENTALIMPURITIES: Proceed as directed in the chapter.

RESIDUALSOLVENTS: Proceed as directed in the chapter.

ORGANICIMPURITIES

Standard solution: USP Amlodipine Besylate CRM and all appropriate USP Impurity RSs, at concentrations corresponding to the

Acceptance criteriaof the impurity, in an appropriate diluentSample solution: Amlodipine Besylate in an appropriate diluent

Analytical system: Use a procedure validated as described in MC general chapterAssessingValidation Parameters for Reference

and Acceptable Procedures .

System performance requirements

Precision:Meets the requirements

Accuracy:Meets the requirements

Ruggedness:Meets the requirements

Specificity:Meets the requirements

Analysis

Samples:Standard solution andSample solution

Calculate the percentage of each impurity in the Sample solution:


rU = response of each impurity from the Sample solution

rS = response of each USP Impurity RS from the Standard solution.[NOTEIf no USP Impurity RSs are available, use

the response of amlodipine.]

CS = concentration of standard material in the Standard solution

CU = concentration of Amlodipine Besylate in the Sample solution

Acceptance criteria

Any individual impurity: NMT 0.10%

Total impurities:NMT 2.0%

SPECIFIC TESTS

WATERDETERMINATION, Method I

Acceptance criteria

Anhydrous: NMT 0.5%

Monohydrate: 3.1%5.0%

ADDITIONAL REQUIREMENTS

REFERENCESTANDARDS

USP Amlodipine Besylate CRM

USP Amlodipine Impurity A RS

(Use USP Amlodipine Related Compound A RS.)

3-Ethyl 5-methyl [2-(2-aminoethoxymethyl)-4-(2-chlorophenyl)-6-methyl-3,5-pyridinedicarboxylate.

USP Amlodipine Impurity B RS

3-Ethyl 5-methyl 4-(2-chlorophenyl)-6-methyl -2-({2-[2-(methylcarbamoyl)benzamido]


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ethoxy}methyl)-1,4-dihydropyridine-3,5-dicarboxylate.

USP Amlodipine Impurity C RS

Dimethyl 4-(2-chlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate.

USP Amlodipine Impurity D RS

3-Ethyl 5-methyl 4-(2-chlorophenyl)-2-{[2-(1,3- dioxoisoindolin-2-yl)ethoxy]methyl}-

6-methyl-1,4-dihydropyridine-3,5-dicarboxylate.

USP Amlodipine Impurity E RS

Diethyl 2-[(2-aminoethoxy)methyl]-4-(2-chlorophenyl)-6-methyl-1,4-dihydropyridine-3,5-dicarboxylate.USP Amlodipine Impurity F RS

Dimethyl 2-[(2-aminoethoxy)methyl]-4-(2-chlorophenyl)-6-methyl-1,4-dihydropyridine-3,5-dicarboxylate.

REFERENCE PROCEDURES

(This section provides detailed descriptions of procedures that may be used for the evaluation of the material under test. These

procedures have been fully validated, and the data is available on the MC website.)

ASSAY

PROCEDURE

Solution A: 10 mM ammonium acetate in water. Adjust with glacial acetic acid to a pH of 5.0.

Solution B:Acetonitrile

Diluent:Water and acetonitrile (3:7)

Mobile phase: See Table 1.

Table 1

Time(min)

Solution A(%)

Solution B(%)

0 90 10

15 90 10

45 30 70

60 90 10

65 90 10

System suitability solution: 0.5 g/mL each of USP Amlodipine Besylate CRM and USP Amlodipine Impurity B RS in Diluent

Standard solution: 0.05 mg/mL of USP Amlodipine Besylate CRM in Diluent

Sample solution: 0.05 mg/mL of Amlodipine Besylate in Diluent

Chromatographic system

(See Chromatography , System Suitability.)

Mode:LCDetector:PDA (scan 200700 nm). [NOTECalculations should be based on the chromatograms collected at 237nm.]

[NOTETo confirm the absence of co-eluting known and unknown impurity peaks, substitute the Reference Procedures, Impurities,

Detector.]

Column: 4.6-mm 25-cm; 5-m packing L11 (similar to Zorbax SB Phenyl)

Flow rate:0.7 mL/min

Temperatures

Column oven:25

Autosampler:5

Injection volume:20 L

System suitability

Samples:System suitability solution andStandard solution

Suitability requirements

Resolution:NLT 1.5 between the amlodipine and impurity B peaks, System suitability solution

Relative standard deviation:NMT 1.0% for the amlodipine besylate peak, Standard solution


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Analysis

Samples:Standard solutionandSample solution

Calculate the percentage of amlodipine besylate (C20H25ClN2O5 C6H6O3S) in the portion of the sample taken:


rU = response of Amlodipine Besylate from the Sample solution

rS = response of amlodipine besylate from the Standard solutionCS = concentration of USP Amlodipine Besylate CRM in the Standard solution. [NOTEThe potency of the Reference

Material is included in this term.]


IMPURITIES

ORGANICIMPURITIES

Solution A, Solution B, Diluent, Mobile phase, andChromatographic system: Proceed as directed in the Reference Procedures,

Assay.

System suitability solution: Proceed as directed for the Standard solutionin the Reference Procedures, Assay.

Standard solution: 0.5 g/mL each of USP Amlodipine Besylate CRM, USP Amlodipine Impurity A RS, USP Amlodipine Impurity B RS,

USP Amlodipine Impurity C RS, USP Amlodipine Impurity D RS, USP Amlodipine Impurity E RS, and USP Amlodipine Impurity F RS in

Diluent

Sample solution: 0.5 mg/mL of Amlodipine Besylate in appropriate Diluent

Detector: PDA and MS

PDA wavelengths: 200700 nm. [NOTEWhere Reference Standards are available a peak maximum wavelength should be

chosen for calculations, otherwise, calculations should be made at an isobestic point of the drug substance and impurity

spectra or at 237 nm if an isobestic point is not available. Impurity F calculations should be done at 360 nm.]

MS source:ES scan (+ and )

MS conditions

Source temperature:80

Desolvation temperature:400

System suitability

Samples:System suitability solution and Standard solution

Suitability requirements

Resolution:NLT 1.5 between the amlodipine and impurity B peaks, Standard solution

Relative standard deviation:NMT 1.0% for the amlodipine besylate peak, System suitability solution

Analysis

Samples:Standard solutionandSample solution

Calculate the percentage of each impurity in the portion of Amlodipine Besylate taken. [NOTEWhere an impurity other than

those included in the Standard solutionis found in the Sample solution, the response and concentration of amlodipine besylate in

the Standard solutionis used for the calculation.]


rU = response of each impurity from the Sample solution

rS = response of each impurity from the Standard solution

CS = concentration of each impurity in the Standard solution.[NOTEThe potency of the Reference Material is

included in this term.]


Source URL (modified on 2013/01/16 - 12:57pm): https://mc.usp.org/monographs/amlodipine-besylate-1-0

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Validasi Zat Aktif Amlodipine Besilate