Donepezil Hydrochloride Tablets
DEFINITION
Donepezil Hydrochloride Tablets contain NLT 93.0% and NMT 107.0% of the labeled amount of donepezil hydrochloride (C24H29NO3·HCl).
IDENTIFICATION
• A. Ultraviolet Absorption 
197U
197U
Wavelength range:
220–360 nm
Sample solution:
Crush a suitable number of Tablets, and transfer an amount of powder, equivalent to 10 mg of donepezil hydrochloride, to a 100-mL volumetric flask. Add 80 mL of 0.1 N hydrochloric acid, and sonicate for 5 min. Cool the solution to room temperature, and dilute with 0.1 N hydrochloric acid to volume. Transfer a portion to a centrifuge tube, and centrifuge for 15 min. Transfer 5 mL of the clear supernatant to a 25-mL volumetric flask, and dilute with 0.1 N hydrochloric acid to volume.
Analysis:
Using a 1-cm cell, record the UV spectrum of the Sample solution.
Acceptance criteria:
The solution exhibits absorption maxima at 230, 271, and 315 nm.
• 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
Diluent:
Methanol and 0.1 N hydrochloric acid (3:1)
Mobile phase:
Dissolve 2.5 g of sodium decanesulfonate in 650 mL of water, and add 1.0 mL of perchloric acid and 350 mL of acetonitrile. If necessary, adjust with an additional 0.5 mL of perchloric acid to a pH of about 1.8.
System suitability solution:
0.2 mg/mL of USP Donepezil Hydrochloride RS and 0.008 mg/mL of USP Donepezil Related Compound A RS. [Note—Dissolve in 40% of the flask volume of methanol, swirl, and dilute with water to volume. ]
Standard solution:
0.4 mg/mL of USP Donepezil Hydrochloride RS in Diluent. [Note—Dissolve in 60% of the flask volume of Diluent, swirl, and dilute with Diluent to volume. ]
Sample solution:
0.4 mg/mL of donepezil hydrochloride in Diluent. [Note—Dissolve a suitable number of Tablets in 75% of the flask volume of Diluent, and sonicate in an ultrasonic bath for 20 min. Swirl the mixture for 30 s, allow to cool to room temperature, and dilute with Diluent to volume. Add a magnetic bar to the flask, and mix for 10 min on a magnetic stirrer. Invert the flask at least 10 times to mix the contents, and then allow a few min for the solids to settle. Pass through a suitable filter, discarding the first 2–3 mL of filtrate. ]
Chromatographic system
Mode:
LC
Detector:
UV 271 nm
Column:
4.6-mm × 15-cm; 5-µm packing L1
Column temperature:
35
Flow rate:
1.4 mL/min
Injection size:
20 µL
System suitability
Samples:
System suitability solution and Standard solution
[Note—The relative retention times for donepezil related compound A and donepezil are about 0.92 and 1.0, respectively. ]
Suitability requirements
Resolution:
NLT 1.5 between donepezil related compound A and donepezil, System suitability solution
Tailing factor:
NMT 1.5 for the donepezil peak, 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 Tablets taken:
Result = (rU/rS) × (CS/CU) × 100
| rU | = | = peak response of donepezil hydrochloride from the Sample solution |
| rS | = | = peak response of donepezil hydrochloride from the Standard solution |
| CS | = | = concentration of USP Donepezil Hydrochloride RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of donepezil hydrochloride in the Sample solution (mg/mL) |
Acceptance criteria:
93.0%–107.0%
PERFORMANCE TESTS
• Dissolution 711
711
Medium:
0.1 N hydrochloric acid; 900 mL
Apparatus 2:
50 rpm
Time:
30 min
Diluent:
Methanol and 0.1 N hydrochloric acid (3:1)
Mobile phase:
Acetonitrile, water, and perchloric acid (350:650:1)
Standard stock solution:
1.1 mg/mL of USP Donepezil Hydrochloride RS in Diluent. Dilute this solution with Medium to obtain a final concentration of 0.11 mg/mL.
Standard solution:
Dilute the Standard stock solution with Medium to obtain a final concentration of L/1000 mg/mL, where L is the Tablet label claim in mg.
Sample solution:
Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size, discarding the first few mL of filtrate.
Chromatographic system
Mode:
LC
Detector:
UV 271 nm
Column:
4.6-mm × 15-cm; 5-µm packing L1
Column temperature:
35
Flow rate:
1.0 mL/min
Injection size:
50 µL
System suitability
Sample:
Standard solution
Suitability requirements
Tailing factor:
NMT 1.5
Column efficiency:
NLT 5000 theoretical plates
Relative standard deviation:
NMT 2.0%
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of donepezil hydrochloride dissolved:
Result = (rU/rS) × (CS/L) × V × 100
| rU | = | = peak response from the Sample solution |
| rS | = | = peak response from the Standard solution |
| CS | = | = concentration of the Standard solution (mg/mL) |
| L | = | = label claim (mg/Tablet) |
| V | = | = volume of Medium, 900 mL |
Tolerances:
NLT 80% (Q) of the labeled amount of donepezil hydrochloride is dissolved.
• Uniformity of Dosage Units 905:
Meet the requirements
905:
Meet the requirements
IMPURITIES
Organic Impurities
• Procedure
Diluent, 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 Diluent
System suitability
Samples:
System suitability solution and Standard solution
[Note—The relative retention times for donepezil related compound A and donepezil are about 0.92 and 1.0, respectively. ]
Suitability requirements
Resolution:
NLT 1.5 between donepezil related compound A and donepezil, System suitability solution
Relative standard deviation:
NMT 8.0%, Standard solution
Analysis
Samples:
Standard solution and Sample solution
[Note—Identify the impurities using the relative retention times given in Impurity Table 1. ]
Calculate the percentage of any individual impurity in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × (1/F) × 100
| rU | = | = peak response of each individual impurity from the Sample solution |
| rS | = | = peak response of donepezil hydrochloride from the Standard solution |
| CS | = | = concentration of USP Donepezil Hydrochloride RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of donepezil hydrochloride in the Sample solution (mg/mL) |
| F | = | = relative response factor (see Impurity Table 1) |
Acceptance criteria
Individual impurities:
See Impurity Table 1.
Impurity Table 1
| Name | Relative Retention Time |
Relative Response Factor |
Acceptance Criteria, NMT (%) |
|---|---|---|---|
| Desbenzyl donepezila | 0.33 | 1.0 | 0.5 |
| Donepezil open ringb | 0.70 | 0.6 | 0.5 |
| Donepezil hydrochloride | 1.0 | — | — |
| Donepezil N- oxidec |
1.2 | 1.0 | 0.5 |
| Any individual unspecified degradation product | — | — | 0.2 |
|
a
5,6-Dimethoxy-2-(piperidin-4-ylmethyl)indan-1-one.
b
2-(3-(1-Benzylpiperidin-4-yl)-2-oxopropyl)-4,5-dimethoxybenzoic acid.
c
2-[(1-Benzylpiperidin-4-yl)methyl]-5,6-dimethoxyindan-1-one N-oxide.
|
|||
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in well-closed containers. Store at controlled room temperature.
• USP Reference Standards 11
11
USP Donepezil Hydrochloride RS 
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USP Donepezil Related Compound A RS
(E)-2-[(1-Benzylpiperidin-4-yl)methylene]-5,6-dimethoxyindan-1-one.
C24H27NO3 377.48
(E)-2-[(1-Benzylpiperidin-4-yl)methylene]-5,6-dimethoxyindan-1-one.
C24H27NO3 377.48
Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
| Topic/Question | Contact | Expert Committee |
|---|---|---|
| Monograph | Ravi Ravichandran, Ph.D.
Principal Scientific Liaison 1-301-816-8330 |
(SM42010) Monographs - Small Molecules 4 |
| 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 2968
Pharmacopeial Forum: Volume No. 36(3) Page 658