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 an Acceptable Procedure is 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. INFRARED ABSORPTION <197M>
B. OPTICAL ROTATION <781A>
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 MC general chapter Assessing Validation Parameters for Reference
and Acceptable Procedures <10>.
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

Analysis
Samples: Standard solution and Sample 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 solution

CS

= concentration of the Standard solution

CU

= concentration of the Sample solution

Acceptance criteria: 98.0%102.0% on the anhydrous basis

IMPURITIES
RESIDUE

ON IGNITION

<281>: NMT 0.1%

ELEMENTAL IMPURITIES <232>: Proceed as directed in the chapter.

RESIDUAL SOLVENTS <467>: Proceed as directed in the chapter.
ORGANIC IMPURITIES
Standard solution: USP Amlodipine Besylate CRM and all appropriate USP Impurity RSs, at concentrations corresponding to the
Acceptance criteria of the impurity, in an appropriate diluent
Sample solution: Amlodipine Besylate in an appropriate diluent
Analytical system: Use a procedure validated as described in MC general chapter Assessing Validation Parameters for Reference
and Acceptable Procedures <10>.
System performance requirements
Precision: Meets the requirements
Accuracy: Meets the requirements
Ruggedness: Meets the requirements
Specificity: Meets the requirements
Analysis
Samples: Standard solution and Sample solution
Calculate the percentage of each impurity in the Sample solution:
Result = (rU/rS) (CS/CU) 100
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
WATER DETERMINATION, Method I <921>
Acceptance criteria
Anhydrous: NMT 0.5%
Monohydrate: 3.1%5.0%
ADDITIONAL REQUIREMENTS
REFERENCE STANDARDS <11>
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]

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
(%)

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 <621>, System Suitability.)
Mode: LC
Detector: 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 and Standard 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

Analysis
Samples: Standard solution and Sample solution
Calculate the percentage of amlodipine besylate (C20H25ClN2O5 C6H6O3S) in the portion of the sample taken:
Result = (rU/rS) (CS/CU) 100
rU

= response of Amlodipine Besylate from the Sample solution

rS

= response of amlodipine besylate from the Standard solution

CS = concentration of USP Amlodipine Besylate CRM in the Standard solution. [NOTEThe potency of the Reference
Material is included in this term.]
CU

= concentration of Amlodipine Besylate in the Sample solution

IMPURITIES
ORGANIC IMPURITIES
Solution A, Solution B, Diluent, Mobile phase, and Chromatographic system: Proceed as directed in the Reference Procedures,
Assay.
System suitability solution: Proceed as directed for the Standard solution in 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 solution and Sample solution
Calculate the percentage of each impurity in the portion of Amlodipine Besylate taken. [NOTEWhere an impurity other than
those included in the Standard solution is found in the Sample solution, the response and concentration of amlodipine besylate in
the Standard solution is used for the calculation.]
Result = (rU/rS) (CS/CU) 100
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.]
CU

= concentration of Amlodipine Besylate in the Sample solution

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