Printed on: Wed Feb 08 2023, 11:48:33 PM(EST) Status: Currently Official on 09-Feb-2023 DocId: GUID-BF41B99E-B619-405D-8604-C8B6BB9E0E1D_5_en-US

Printed by: Dang Van Vu Official Date: Official as of 01-May-2021 Document Type: USP @2023 USPC
Do Not Distribute DOI Ref: u3uae DOI: https://doi.org/10.31003/USPNF_M125_05_01
1

rS = peak response of acebutolol from the Standard

Acebutolol Hydrochloride solution
CS = concentration of USP Acebutolol Hydrochloride
RS in the Standard solution (mg/mL)
CU = concentration of Acebutolol Hydrochloride in the
Sample solution (mg/mL)

Acceptance criteria: 98.0%–102.0% on the dried basis

C18H28N2O4 · HCl 372.89
Butanamide, N-[3-acetyl-4-[2-hydroxy-3-[(1-methylethyl) IMPURITIES
amino]propoxy]phenyl]-, monohydrochloride, (±)-; • RESIDUE ON IGNITION á281ñ: NMT 0.1%
(±)-3′-Acetyl-4′-[2-hydroxy-3-(isopropylamino)propoxy]-
butyranilide monohydrochloride CAS RN®: 34381-68-5; Change to read:
UNII: B025Y34C54.
• ORGANIC IMPURITIES
DEFINITION Solution A: Mix 2.0 mL of phosphoric acid and 3.0 mL of
Acebutolol Hydrochloride contains NLT 98.0% and NMT triethylamine, and dilute with water to 1 L.
102.0% of acebutolol hydrochloride (C18H28N2O4 · HCl), Solution B: Acetonitrile and Solution A (50:50)
calculated on the dried basis. Mobile phase: See Table 1.
IDENTIFICATION Table 1
• A. SPECTROSCOPIC IDENTIFICATION TESTS á197ñ, Infrared
Spectroscopy: 197K Time Solution A Solution B
(min) (%) (%)
• B. The retention time of the major peak of the Sample

al
solution corresponds to that of the Standard solution, as 0 98 2
obtained in the Assay. 2 98 2

Change to read: ci 30.5 10 90

41 10 90
• C. IDENTIFICATION TESTS—GENERAL á191ñ, Chemical
Identification Tests, Chloride: Meets the requirements of
▲
the test for amine hydrochlorides▲ (USP 1-May-2021) Standard stock solution 1: 0.2 mg/mL of USP Acebutolol
Related Compound A RS prepared as follows. Dissolve a
ASSAY suitable amount of USP Acebutolol Related Compound A
ffi
Change to read:
RS in a suitable volumetric flask, in 50% of the total volume
of acetonitrile, and dilute with Solution A to volume.
• PROCEDURE Standard stock solution 2: 0.2 mg/mL of USP Acebutolol
Mobile phase: Methanol, glacial acetic acid, and a 0.3% Related Compound B RS prepared as follows. Dissolve a
aqueous solution of sodium dodecyl sulfate (675:20:325) suitable amount of USP Acebutolol Related Compound B
▲
▲ (USP 1-May-2021)
RS in a suitable volumetric flask, in 50% of the total volume
O

Standard solution: 0.14 mg/mL of USP Acebutolol of acetonitrile, and dilute with Solution A to volume.
Hydrochloride RS in water Standard solution A: 0.002 mg/mL of USP Acebutolol
Sample solution: 0.14 mg/mL of Acebutolol Hydrochloride Hydrochloride RS in Solution A
in water Standard solution B: 0.004 mg/mL of USP Acebutolol
Chromatographic system Related Compound I RS in Solution A
(See Chromatography á621ñ, System Suitability.) Standard solution C: 0.002 mg/mL of USP Acebutolol
Mode: LC Related Compound A RS in Solution A from Standard stock
Detector: UV 254 nm solution 1
Column: 3.9-mm × 30-cm; ▲10-µm▲ (USP 1-May-2021) packing Standard solution D: 0.004 mg/mL of USP Acebutolol
L1 Related Compound B RS in Solution A from Standard stock
Flow rate: 2 mL/min solution 2
Injection volume: 10 µL System suitability solution: 0.4 µg/mL each of USP
System suitability Acebutolol Hydrochloride RS and USP Acebutolol Related
Sample: Standard solution Compound I RS in Solution A from Standard solution A and
Suitability requirements Standard solution B
▲
▲ (USP 1-May-2021)
Sample solution: 2 mg/mL of Acebutolol Hydrochloride in
Tailing factor: NMT 2.5 Solution A
Relative standard deviation: ▲NMT▲ (USP 1-May-2021) Chromatographic system
0.73% (See Chromatography á621ñ, System Suitability.)
Analysis Mode: LC
Samples: Standard solution and Sample solution Detector: UV 240 nm
Calculate the percentage of acebutolol hydrochloride Column: 4.0-mm × 12.5-cm; 5-µm packing L1
(C18H28N2O4 · HCl) in the portion of Acebutolol Column temperature: 40°
Flow rate: 1.2 mL/min
Hydrochloride taken:
Injection volume: 25 µL
Result = (rU/rS) × (CS/CU) × 100 System suitability
Samples: Standard solution A and System suitability solution
rU = peak response of acebutolol from the Sample Suitability requirements
solution Resolution: NLT 7.0 between acebutolol and acebutolol
related compound I, System suitability solution

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Printed on: Wed Feb 08 2023, 11:48:33 PM(EST) Status: Currently Official on 09-Feb-2023 DocId: GUID-BF41B99E-B619-405D-8604-C8B6BB9E0E1D_5_en-US
Printed by: Dang Van Vu Official Date: Official as of 01-May-2021 Document Type: USP @2023 USPC
Do Not Distribute DOI Ref: u3uae DOI: https://doi.org/10.31003/USPNF_M125_05_01
2

Relative standard deviation: NMT 2.0%, Standard Table 2 (continued)

solution A Relative Acceptance
Analysis Retention Criteria,
Samples: Standard solution A, Standard solution B, Standard Name Time NMT (%)
solution C, Standard solution D, and Sample solution Acebutolol related
Calculate the percentage of acebutolol related compound compound I▲▲
A, acebutolol related compound B, and acebutolol related (USP 1-May-2021) 0.91 0.2
compound I in the portion of Acebutolol Hydrochloride Acebutolol 1.00 —
taken:
Acebutolol related
Result = (rU/rS) × (CS/CU) × 100 compound A▲▲
(USP 1-May-2021) 1.48 0.1
rU = peak response of acebutolol related compound A, Any unspecified impuri-
—
acebutolol related compound B, or acebutolol ty 0.10
related compound I from the Sample solution
Total impuritiesa — 0.5
rS = peak response of acebutolol related compound A,
acebutolol related compound B, or acebutolol a Total impurities include specified and unspecified impurities.▲
▲ (USP 1-May-2021)
related compound I from Standard solution B,
Standard solution C, or Standard solution D SPECIFIC TESTS
CS = concentration of USP Acebutolol Related • PH á791ñ
Compound A RS, USP Acebutolol Related Sample solution: 10 mg/mL of Acebutolol Hydrochloride
Compound B RS, or USP Acebutolol Related in water
Compound I RS in Standard solution B, Standard

al
Acceptance criteria: 4.5–7.0
solution C, or Standard solution D (mg/mL) • LOSS ON DRYING á731ñ
CU = concentration of Acebutolol Hydrochloride in the Analysis: Dry at 105° for 3 h.
Sample solution (mg/mL) Acceptance criteria: NMT 1.0%
Calculate the percentage of any unspecified impurity in the ADDITIONAL REQUIREMENTS
portion of Acebutolol Hydrochloride taken:

Result = (rU/rS) × (CS/CU) × 100

ci • PACKAGING AND STORAGE: Preserve in tight containers, and
store at controlled room temperature.
• USP REFERENCE STANDARDS á11ñ
USP Acebutolol Hydrochloride RS
rU = peak response of any unspecified impurity from USP Acebutolol Related Compound A RS
ffi
the Sample solution N-(3-Acetyl-4-hydroxyphenyl)butyramide.
rS = peak response of acebutolol from Standard C12H15NO3 221.25
solution A USP Acebutolol Related Compound B RS
CS = concentration of USP Acebutolol Hydrochloride N-{3-Acetyl-4-[2-hydroxy-3-(isopropylamino)propoxy]
RS in Standard solution A (mg/mL) phenyl}acetamide.
CU = concentration of Acebutolol Hydrochloride in the C16H24N2O4 308.37
O

Sample solution (mg/mL) USP Acebutolol Related Compound I RS

N-{3-Acetyl-4-[3-(ethylamino)-2-hydroxypropoxy]
Acceptance criteria: See Table 2. ▲The reporting phenyl}butyramide.
threshold is▲ (USP 1-May-2021) 0.05%. C17H26N2O4 322.40
Table 2
Relative Acceptance
Retention Criteria,
Name Time NMT (%)
Acebutolol related
compound B▲▲
(USP 1-May-2021) 0.72 0.2

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