Amlodipine Besylate Tablets
DEFINITION
Amlodipine Besylate Tablets contain NLT 90% and NMT 110% of the labeled amount of amlodipine (C20H25N2O5Cl).
IDENTIFICATION
• A. Ultraviolet Absorption 
197U
197U
Standard solution and Sample solution:
Prepare as directed in the test for Dissolution.
Acceptance criteria:
Meet the requirements
• 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:
Add 7.0 mL of triethylamine into a 1000-mL flask containing 900 mL of water. Adjust the solution with phosphoric acid to a pH of 3.0 ± 0.1. Dilute with water to volume, and mix well.
Mobile phase:
Methanol, acetonitrile, and Buffer (35:15:50)
System suitability solution:
0.02 mg/mL of USP Amlodipine Besylate RS and 0.002 mg/mL of USP Amlodipine Related Compound A RS in Mobile phase
Standard solution:
0.02 mg/mL of amlodipine prepared from USP Amlodipine Besylate RS in Mobile phase
Sample stock solution:
Place 5 Tablets into a 500-mL volumetric flask. Add 50 mL of Mobile phase to the flask, and swirl to disintegrate the Tablets. Add 300 mL of Mobile phase, insert the stopper into the flask, and shake on a reciprocating shaker for 30 min. Dilute with Mobile phase to volume, and mix well.
Sample solution:
0.02 mg/mL of amlodipine from the Sample stock solution in Mobile phase. Pass the sample through a syringe tip filter of 0.45-µm pore size.
Chromatographic system
Mode:
LC
Detector:
UV 237 nm
Column:
3.9-mm × 15-cm; 5-µm packing L1
Flow rate:
1 mL/min
Injection size:
50 µL
System suitability
Sample:
System suitability solution
[Note—The run time is about three times the retention of the amlodipine peak. ]
Suitability requirements
Resolution:
NLT 8.5 between amlodipine and amlodipine related compound A
Tailing factor:
NMT 2.0 for both amlodipine and amlodipine related compound A
Relative standard deviation:
NMT 1.0% for amlodipine and NMT 5.0% for amlodipine related compound A
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of the labeled amount of amlodipine (C20H25N2O5Cl) 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 USP Amlodipine Besylate RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of amlodipine in the Sample solution (mg/mL) |
Acceptance criteria:
90%–110% of the labeled amount of amlodipine (C20H25N2O5Cl)
PERFORMANCE TESTS
• Dissolution 711
711
[Note—Do not expose any of the solutions to stainless steel because of the degradation of amlodipine. ]
Medium:
0.01 N hydrochloric acid; 500 mL
Apparatus 2:
75 rpm. [Note—Use paddles covered with Teflon or made of any inert material except stainless steel. ]
Time:
30 min
Standard solution:
Make appropriate dilutions of USP Amlodipine Besylate RS in Medium to obtain the following concentrations: 0.00695 mg/mL for Tablets labeled to contain 2.5 mg; 0.0139 mg/mL for Tablets labeled to contain 5 mg; 0.0278 mg/mL for Tablets labeled to contain 10 mg. These solutions are stable for one day.
Sample solution:
Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size.
Analysis:
Determine the amount of amlodipine (C20H25N2O5Cl) dissolved by using UV absorption at the wavelength of maximum absorbance at about 239 nm on portions of the Sample solution in comparison with the Standard solution, using a 1-cm quartz cell and the Medium as blank.
Calculate the percentage of the labeled amount of amlodipine (C20H25ClN2O5) dissolved:
Result = (AU/AS) × (CS/L) × D × (Mr1/Mr2) × V × 100
| AU | = | = absorbance of the Sample solution |
| AS | = | = absorbance of the Standard solution |
| CS | = | = concentration of the Standard solution (mg/mL) |
| L | = | = label claim (mg/Tablet) |
| D | = | = dilution factor of the Sample solution |
| Mr1 | = | = molecular weight of amlodipine, 408.88 |
| Mr2 | = | = molecular weight of amlodipine besylate, 567.06 |
| V | = | = volume of Medium, 500 mL |
Tolerances:
NLT 75% (Q) of the labeled amount of amlodipine (C20H25N2O5Cl) is dissolved.
• Uniformity of Dosage Units 905:
Meet the requirements
905:
Meet the requirements
IMPURITIES
• Organic Impurities
Buffer, Mobile phase, System suitability solution, Chromatographic system, and System suitability:
Proceed as directed in the Assay.
Standard solution:
Use the System suitability solution.
Sample solution:
Place a suitable number of Tablets into a 25-mL volumetric flask to obtain a solution having a final nominal concentration of 0.4 mg/mL of amlodipine. Add about 10 mL of Mobile phase to the flask. Swirl to disintegrate the Tablet(s), followed by sonication for 5 min to completely dissolve, and then cool the sample to room temperature. Dilute with Mobile phase to volume. Stir for an additional 15 min using a magnetic stir bar, and pass the sample through a syringe tip filter of 0.45-µm pore size, discarding the first 5 mL.
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of amlodipine related compound A in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × (Mr1/Mr2) × 100
| rU | = | = peak response of amlodipine related compound A from the Sample solution |
| rS | = | = peak response of amlodipine related compound A from the Standard solution |
| CS | = | = concentration of USP Amlodipine Related Compound A RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of amlodipine in the Sample solution (mg/mL) |
| Mr1 | = | = molecular weight of amlodipine related compound A, 406.86 |
| Mr2 | = | = molecular weight of amlodipine related compound A fumarate, 522.93 |
Calculate the percentage of amlodipine glucose/galactose adduct or amlodipine lactose adduct, if present, in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × (Mr1/Mr2) × 100
| rU | = | = peak response of the amlodipine glucose/galactose adduct or amlodipine lactose adduct in the Sample solution |
| rS | = | = peak response of amlodipine in the Standard solution |
| CS | = | = concentration of USP Amlodipine Besylate RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of amlodipine in the Sample solution (mg/mL) |
| Mr1 | = | = molecular weight of amlodipine, 408.9 |
| Mr2 | = | = molecular weight of amlodipine besylate, 567.05 |
Calculate the percentage of any other individual unspecified degradation product 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 amlodipine from the Standard solution |
| CS | = | = concentration of amlodipine in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of amlodipine in the Sample solution (mg/mL) |
Acceptance criteria:
See Table 1.
Table 1
| Name | Relative Retention Time |
Acceptance Criteria, NMT (%) |
|
|---|---|---|---|
| Amlodipine related compound Aa | 0.50 | 1.0 | |
| Amlodipine lactose adductb | 0.80 | 0.5 | |
| Amlodipine glucose/galactose adductb | 0.90 | 0.5 | |
| Amlodipine besylate | 1.0 | — | |
| Any other individual unspecified degradation product | — | 0.20 | |
|
a
3-Ethyl, 5-methyl [2-(2-aminoethoxymethyl)-4-(2-chlorophenyl)-6-methyl-3,5-pyridinedicarboxylate].
b
Formulation-specific impurities.
|
|||
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in tight, light-resistant containers. Store at controlled room temperature.
• USP Reference Standards 11
11
USP Amlodipine Besylate RS 
') + '&img=../../images/v35300/cas-111470-99-6.gif',600,500);)
USP Amlodipine Related Compound A RS
3-Ethyl, 5-methyl [2-(2-aminoethoxymethyl)-4-(2-chlorophenyl)-6-methyl-3,5-pyridinedicarboxylate fumarate.
C20H23ClN2O5·C4H4O4 522.93
') + '&img=../../images/v35300/c11rs4038.gif',600,500);)
3-Ethyl, 5-methyl [2-(2-aminoethoxymethyl)-4-(2-chlorophenyl)-6-methyl-3,5-pyridinedicarboxylate fumarate.
C20H23ClN2O5·C4H4O4 522.93
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 2187
Pharmacopeial Forum: Volume No. 36(2) Page 376