Printed on: Thu Jan 13 2022, 02:30:17 AM(EST) Official Status: Currently Official on 13-Jan-2022 DocId: 1_GUID-8FA69715-A1F2-468C-BA6E-399B1AAA2B38_8_en-US

Printed by: Chalai Promla Official Date: Official as of 01-May-2021 Document Type: USP @2022 USPC
DOI Ref: dxd5q DOI: https://doi.org/10.31003/USPNF_M3575_08_01
1

Calculate the percentage of the labeled amount of

Amlodipine Besylate Tablets amlodipine (C20H25ClN2O5) in the portion of Tablets
DEFINITION taken:

Change to read: Result = (rU/rS) × (CS/CU) × (Mr1/Mr2) × 100

Amlodipine Besylate Tablets contain ▲an amount of rU = peak response of amlodipine from the Sample
amlodipine besylate equivalent to▲ (USP 1-May-2021) NLT 90% solution
and NMT 110% of the labeled amount of amlodipine rS = peak response of amlodipine from the Standard
(C20H25ClN2O5). solution
CS = concentration of USP Amlodipine Besylate RS in
IDENTIFICATION the Standard solution (mg/mL)
Change to read: CU = nominal concentration of amlodipine in the
Sample solution (mg/mL)
• A. ▲The UV spectra of the major peak of the Sample Mr1 = molecular weight of amlodipine, 408.88
solution correspond to those of the Standard solution, as Mr2 = molecular weight of amlodipine besylate, 567.05
obtained in the Assay.▲ (USP 1-May-2021)
• B. The retention time of the major peak of the Sample Acceptance criteria: 90%–110%▲▲ (USP 1-May-2021)
solution corresponds to that of the Standard solution, as
obtained in the Assay. PERFORMANCE TESTS

ASSAY Change to read:

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Change to read: • DISSOLUTION á711ñ
[NOTE—Do not expose any of the solutions to stainless
• PROCEDURE steel because of the degradation of amlodipine.]
Buffer: Add 7.0 mL of triethylamine into a 1000-mL flask ▲
Test 1▲ (USP 1-May-2021)
containing 900 mL of water. Adjust the solution with Medium: 0.01 N hydrochloric acid; 500 mL
phosphoric acid to a pH of 3.0.▲▲ (USP 1-May-2021) Dilute with Apparatus 2: 75 rpm. [NOTE—Use paddles covered with
water to volume, and mix well.
Mobile phase: Methanol, acetonitrile, and Buffer
(35:15:50)
ci Teflon or made of any inert material except stainless steel.]
Time: 30 min
Standard solution: ▲(L/360) mg/mL of USP Amlodipine
Standard solution: 0.0275 mg/mL of USP Amlodipine Besylate RS in Medium, where L is the label claim of
Besylate RS and 0.0025 mg/mL of USP Amlodipine Related amlodipine in mg/Tablet. [NOTE—These solutions are
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Compound A RS in Mobile phase stable for 1 day.]▲ (USP 1-May-2021)
Sample solution: Nominally 0.02 mg/mL of amlodipine in Sample solution: Pass a portion of the solution under test
Mobile phase prepared as follows. Place Tablets (NLT 5) in a through a suitable filter of 0.45-µm pore size.
suitable volumetric flask, and add a sufficient quantity of Blank: Medium
Mobile phase to disintegrate the Tablets. Shake for 30 min, Instrumental conditions
and dilute with Mobile phase to volume. Pass the sample Mode: UV
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through a syringe tip filter of 0.45-µm pore size. Discard the Analytical wavelength: 239 nm
first few milliliters of the filtrate. Cell: 1-cm quartz
Chromatographic system Analysis
(See Chromatography á621ñ, System Suitability.) Samples: Standard solution and Sample solution
Mode: LC ▲
▲ (USP 1-May-2021)
Detector: UV 237 nm. ▲For Identification A, use a diode Calculate the percentage of the labeled amount of
array detector in the range of 200–400 nm.▲ (USP 1-May-2021) amlodipine (C20H25ClN2O5) dissolved:
Column: 3.9-mm × 15-cm; ▲4- or▲ (USP 1-May-2021) 5-µm
packing L1 Result = (AU/AS) × CS × V ▲▲ (USP 1-May-2021) × (Mr1/Mr2) × (1/
Flow rate: 1 mL/min L) × 100
Injection volume: 50 µL
Run time: NLT 3 times the retention ▲time▲ (USP 1-May-2021) AU = absorbance of amlodipine from the Sample
of amlodipine solution
System suitability AS = absorbance of amlodipine from the Standard
Sample: Standard solution solution
[NOTE—The relative retention times for amlodipine CS = concentration of ▲USP Amlodipine
related compound A and amlodipine are about Besylate RS▲ (USP 1-May-2021) in the Standard solution
0.5 and 1.0, respectively.] (mg/mL)
Suitability requirements V = volume of Medium, 500 mL
Resolution: NLT 8.5 between amlodipine related ▲
▲ (USP 1-May-2021)
compound A and amlodipine Mr1 = molecular weight of amlodipine, 408.88
Tailing factor: NMT 2.0 for amlodipine related Mr2 = molecular weight of amlodipine besylate, 567.05
compound A and amlodipine L = label claim (mg/Tablet)
Relative standard deviation: NMT 5.0% for amlodipine
related compound A ▲and NMT 2.0% for Tolerances: NLT 75% (Q) of the labeled amount of
amlodipine▲ (USP 1-May-2021) amlodipine (C20H25ClN2O5) is dissolved.
Analysis ▲
Test 2: If the product complies with this test, the labeling
Samples: Standard solution and Sample solution indicates that it meets USP Dissolution Test 2.
Medium, Apparatus 2, and Time: Proceed as directed in
Test 1.

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Printed on: Thu Jan 13 2022, 02:30:17 AM(EST) Official Status: Currently Official on 13-Jan-2022 DocId: 1_GUID-8FA69715-A1F2-468C-BA6E-399B1AAA2B38_8_en-US
Printed by: Chalai Promla Official Date: Official as of 01-May-2021 Document Type: USP @2022 USPC
DOI Ref: dxd5q DOI: https://doi.org/10.31003/USPNF_M3575_08_01
2

Buffer A: Dissolve 1.36 g of potassium phosphate, 5 min to completely dissolve, and cool to room
monobasic in 1000 mL of water. Add 5 mL of temperature. Dilute with Mobile phase to volume. Stir for
triethylamine and adjust the solution with phosphoric acid an additional 15 min using a magnetic stir bar, and pass the
to a pH of 2.0. sample through a syringe tip filter of 0.45-µm pore size,
Buffer B: Dilute 7.0 mL of triethylamine in 1000 mL of discarding the first 5 mL.
water. Adjust the solution with phosphoric acid to a pH of System suitability
3.0. Samples: Standard solution▲ and Sensitivity
Mobile phase: Acetonitrile and Buffer A (30:70) solution▲ (USP 1-May-2021)
Diluent: Acetonitrile, methanol, and Buffer B (15:35:50) Suitability requirements: Proceed as directed in the Assay
Standard stock solution: 0.693 mg/mL of USP ▲
except for Signal-to-noise ratio.
Amlodipine Besylate RS in Diluent Signal-to-noise ratio: NLT 10, Sensitivity
Standard solution: (L/361) mg/mL of USP Amlodipine solution▲ (USP 1-May-2021)
Besylate RS in Medium, where L is the label claim of Analysis
amlodipine in mg/Tablet Samples: Standard solution and Sample solution
Sample solution: Centrifuge a portion of the solution Calculate the percentage of amlodipine related
under test for 5 min. compound A ▲(free base)▲ (USP 1-May-2021) in the portion of
Chromatographic system Tablets taken:
(See Chromatography á621ñ, System Suitability.)
Mode: LC Result = (rU/rS) × (CS/CU) × (Mr1/Mr2) × 100
Detector: UV 237 nm
Column: 4.6-mm × 15-cm; 5-µm packing L1 rU = peak response of amlodipine related compound A
Temperatures from the Sample solution
rS = peak response of amlodipine related compound A

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Autosampler: 5°
Column: 35° from the Standard solution
Flow rate: 1.5 mL/min CS = concentration of USP Amlodipine Related
Injection volume: 20 µL Compound A RS in the Standard solution
Run time: NLT 1.7 times the retention time of amlodipine (mg/mL)
System suitability CU = nominal concentration of amlodipine in the
Sample: Standard solution
Suitability requirements
Tailing factor: NMT 2.0
ci Mr1
Sample solution (mg/mL)
= molecular weight of amlodipine related
compound A ▲(free base),▲ (USP 1-May-2021) 406.86
Relative standard deviation: NMT 2.0% Mr2 = molecular weight of amlodipine related
Analysis compound A, ▲522.94▲ (USP 1-May-2021)
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Samples: Standard solution and Sample solution
Calculate the percentage of the labeled amount of Calculate the percentage of amlodipine glucose/galactose
amlodipine (C20H25ClN2O5) dissolved: adduct or amlodipine lactose adduct, if present, and any
unspecified degradation product in the portion of Tablets
Result = (rU/rS) × CS × V × (Mr1/Mr2) × (1/L) × 100 taken:
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rU = peak response of amlodipine from the Sample Result = (rU/rS) × (CS/CU) × (Mr1/Mr2) × 100
solution
rS = peak response of amlodipine from the Standard rU = peak response of amlodipine glucose/galactose
solution adduct, amlodipine lactose adduct, or any
CS = concentration of USP Amlodipine Besylate RS in unspecified degradation product from the
the Standard solution (mg/mL) Sample solution
V = volume of Medium, 500 mL rS = peak response of amlodipine from the Standard
Mr1 = molecular weight of amlodipine, 408.88 solution
Mr2 = molecular weight of amlodipine besylate, 567.05 CS = concentration of USP Amlodipine Besylate RS
L = label claim (mg/Tablet) from the Standard solution (mg/mL)
CU = nominal concentration of amlodipine in the
Tolerances: NLT 80% (Q) of the labeled amount of Sample solution (mg/mL)
amlodipine (C20H25ClN2O5) is dissolved.▲ (USP 1-May-2021) Mr1 = molecular weight of amlodipine,
• UNIFORMITY OF DOSAGE UNITS á905ñ: Meet the
▲
408.88▲ (USP 1-May-2021)
requirements Mr2 = molecular weight of amlodipine besylate, 567.05
IMPURITIES Acceptance criteria: See Table 1.
Change to read:
Table 1
• ORGANIC IMPURITIES Relative Acceptance
Buffer, Mobile phase, Standard solution, and Retention Criteria,
Name Time NMT (%)
Chromatographic system: Proceed as directed in the
Assay. ▲
Benzenesulfonic acida 0.15 —▲ (USP 1-May-2021)
▲
Sensitivity solution: 0.55 μg/mL of USP Amlodipine
Amlodipine related
Besylate RS in Mobile phase▲ (USP 1-May-2021) compound Ab 0.50 1.0
Sample solution: ▲Nominally 0.4 mg/mL of amlodipine in
Mobile phase prepared as follows.▲ (USP 1-May-2021) Place a Amlodipine lactose ad-
ductc 0.80 0.5
suitable number of Tablets in a 25-mL volumetric flask.
▲ (USP 1-May-2021) Add about 10 mL of Mobile phase to the
▲
Amlodipine glucose/
flask. Swirl to disintegrate the Tablets, then sonicate for galactose adductc 0.90 0.5

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Printed on: Thu Jan 13 2022, 02:30:17 AM(EST) Official Status: Currently Official on 13-Jan-2022 DocId: 1_GUID-8FA69715-A1F2-468C-BA6E-399B1AAA2B38_8_en-US
Printed by: Chalai Promla Official Date: Official as of 01-May-2021 Document Type: USP @2022 USPC
DOI Ref: dxd5q DOI: https://doi.org/10.31003/USPNF_M3575_08_01
3

Table 1 (continued) Add the following:

Relative Acceptance
Retention Criteria, ▲
• LABELING: When more than one Dissolution test is given,
Name Time NMT (%) the labeling states the Dissolution test used only if Test 1 is
Amlodipine ▲▲ not used.▲ (USP 1-May-2021)
—
(USP 1-May-2021) 1.0
Change to read:
Any unspecified degra-
—
dation product 0.2
• USP REFERENCE STANDARDS á11ñ
▲
Total impurities — 1.5▲ (USP 1-May-2021) USP Amlodipine Besylate RS
USP Amlodipine Related Compound A RS
▲a
This peak is due to the counterion and is not to be reported or included in 3-Ethyl 5-methyl [2-(2-aminoethoxymethyl)-4-(2-
the total impurities.▲ (USP 1-May-2021) chlorophenyl)-6-methyl-3,5-pyridinedicarboxylate]
b 3-Ethyl 5-methyl [2-(2-aminoethoxymethyl)-4-(2-chlorophenyl)-6-methyl-
3,5-pyridinedicarboxylate].▲▲ (USP 1-May-2021)
fumarate.
c Formulation-specific impurities. C20H23ClN2O5 · C4H4O4 ▲522.94▲ (USP 1-May-2021)

ADDITIONAL REQUIREMENTS
• PACKAGING AND STORAGE: Preserve in tight, light-resistant
containers. Store at controlled room temperature.

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