Donepezil Hydrochloride
(doe nep' e zil hye'' droe klor' ide).
C24H29NO3·HCl 415.95 (±)-2-[(1-Benzyl-4-piperidyl)methyl]-5,6-dimethoxy-1-indanone hydrochloride ![]() ![]() ![]() DEFINITION
Donepezil Hydrochloride contains NLT 98.0% and NMT 102.0% of C24H29NO3·HCl, calculated on the anhydrous basis.
IDENTIFICATION
Change to read:
• A. Infrared Absorption ![]() ![]() ![]() ![]()
• B.
The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.
• C. Identification Tests—General, Chloride
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Sample solution:
10 mg/mL
Acceptance criteria:
Meets the requirements
ASSAY
• Procedure
Buffer:
3.9 g/L of sodium 1-decane sulfonate in water
Mobile phase:
Acetonitrile and Buffer (35:65). Adjust with perchloric acid to a pH of 1.8.
System suitability solution:
0.4 mg/mL of USP Donepezil Hydrochloride RS and 0.016 mg/mL of USP Donepezil Related Compound A RS prepared as follows. Dissolve suitable quantities of USP Donepezil Hydrochloride RS and USP Donepezil Related Compound A RS using 40% of the flask volume of methanol, and dilute with water to volume.
Standard solution:
0.4 mg/mL of USP Donepezil Hydrochloride RS in Mobile phase
Sample solution:
0.4 mg/mL of Donepezil Hydrochloride in Mobile phase
Chromatographic system
Mode:
LC
Detector:
UV 271 nm
Column:
4.6-mm × 15-cm; 5-µm packing L1
Column temperature:
35
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Flow rate:
1.4 mL/min
Injection size:
20 µL
System suitability
Samples:
System suitability solution and Standard solution
[Note—Refer to Table 1 under Organic Impurities, Procedure 1 for the relative retention times. ]
Suitability requirements
Resolution:
NLT 1.5 between donepezil related compound A and donepezil, System suitability solution
Relative standard deviation:
NMT 2.0%, Standard solution
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of donepezil hydrochloride (C24H29NO3·HCl) in the portion of sample taken:
Result = (rU/rS) × (CS/CU) × 100
Acceptance criteria:
98.0%–102.0% on the anhydrous basis
IMPURITIES
• Heavy Metals, Method II
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• Residue on Ignition
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Change to read:
• Organic Impurities, ![]()
[Note—On the basis of the synthetic route, perform either Procedure 1 or Procedure 2. Procedure 2 is recommended if any of the impurities included in Table 3 are potential related compounds. ]
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Mobile phase, System suitability solution, Sample solution, and Chromatographic system:
Proceed as directed in the Assay.
Standard solution:
0.8 µg/mL of USP Donepezil Hydrochloride RS in Mobile phase
System suitability
Samples:
System suitability solution and Standard solution
[Note—Refer to Table 1 for the relative retention times. ]
Suitability requirements
Resolution:
NLT 1.5 between donepezil related compound A and donepezil, System suitability solution
Relative standard deviation:
NLT 5.0%, Standard solution
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of any individual impurity in the portion of Donepezil Hydrochloride taken:
Result = (rU/rS) × (CS/CU) × 100
Acceptance criteria:
See Table 1.
Table 1
Add the following:
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Diluent:
Acetonitrile and water (25:75)
Solution A:
Add 1 mL of phosphoric acid in 1 L of water. Adjust with triethylamine to a pH of 6.5. Pass through a filter of 0.45-µm or finer pore size.
Solution B:
Acetonitrile
Mobile phase:
See Table 2.
Table 2
Standard solution:
0.01 mg/mL of USP Donepezil Hydrochloride RS in Diluent. Sonication may be used to aid the dissolution.
Sample solution:
1.0 mg/mL of Donepezil Hydrochloride in Diluent. Sonication may be used to aid the dissolution.
Chromatographic system
Mode:
LC
Detector:
UV 286 nm
Column:
4.6-mm × 25-cm; 5-µm packing L1
Column temperature:
50
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Flow rate:
1.5 mL/min
Injection size:
20 µL
System suitability
Sample:
Standard solution
Suitability requirements
Column efficiency:
NLT 40,000 theoretical plates
Tailing factor:
NMT 1.5
Relative standard deviation:
NMT 2.0%, for five replicate injections
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of any individual impurity in the portion of Donepezil Hydrochloride taken:
Result = (rU/rS) × (CS/CU) × (1/F) × 100
Acceptance criteria:
See Table 3.
Table 3
![]() SPECIFIC TESTS
Change to read:
• Water Determination, Method Ia ![]() ![]() ![]() ![]() ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in well-closed containers. Store at controlled room temperature.
Add the following:
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Change to read:
• USP Reference Standards ![]() ![]()
USP Donepezil Related Compound A RS
![]() ![]() C24H27NO3 377.48
Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
USP35–NF30 Page 2967
Pharmacopeial Forum: Volume No. 36(1) Page 97
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