Levetiracetam Tablets
711
Test 1(RB 1-May-2011)
Test 2:
If the product complies with this test, the labeling indicates that the product meets USP Dissolution Test 2.
• Labeling:
When more than one Dissolution test is given, the labeling states the Dissolution test used only if Test 1 is not used.(RB 1-May-2011)
DEFINITION
Levetiracetam Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of levetiracetam (C8H14N2O2).
IDENTIFICATION
• 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:
1.4 g/L of monobasic potassium phosphate and 0.6 g/L of sodium 1-heptanesulfonate, adjusted with phosphoric acid to a pH of 2.8
Mobile phase:
Acetonitrile and Buffer (8:92)
Diluent:
Acetonitrile and water (20:80)
Standard solution:
0.35 mg/mL of USP Levetiracetam RS in Diluent. Sonication may be used to aid dissolution.
Sample solution:
Nominally 0.4 mg/mL of levetiracetam from NLT 20 Tablets, finely crushed, in Diluent. Sonication may be used to aid dissolution.
Chromatographic system
Mode:
LC
Detector:
UV 220 nm
Column:
4.6-mm × 25-cm; 4-µm packing L1
Flow rate:
2 mL/min
Injection size:
10 µL
System suitability
Sample:
Standard solution
Suitability requirements
Tailing factor:
NMT 2.0
Relative standard deviation:
NMT 2.0%
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of levetiracetam (C8H14N2O2) 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 Levetiracetam RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of levetiracetam in the Sample solution (mg/mL) |
Acceptance criteria:
90.0%–110.0%
PERFORMANCE TESTS
Change to read:
• Dissolution 711
Test 1(RB 1-May-2011)
Medium:
Water; 900 mL
Apparatus 2:
50 rpm
Buffer:
6.8 g/L of monobasic potassium phosphate, adjusted with dilute potassium hydroxide to a pH of 5.6
Mobile phase:
Acetonitrile and Buffer (15:85)
Standard solution:
(L/1000) mg/mL in Medium, where L is the Tablet label claim, in mg
Sample solution:
Pass a portion of the solution under test though a suitable filter of 0.45-µm pore size.
Chromatographic system
Mode:
LC
Detector:
UV 220 nm
Column:
4.6-mm × 15-cm; 5-µm packing L1
Flow rate:
1.2 mL/min
Injection size:
10 µL
System suitability
Sample:
Standard solution
Suitability requirements
Tailing factor:
NMT 2.0
Relative standard deviation:
NMT 2.0%
Analysis
Samples:
Standard solution and Sample solution
Determine the percentage of levetiracetam ( C8H14N2O2) 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 USP Levetiracetam RS in the Standard solution (mg/mL) |
| L | = | = label claim (mg/Tablet) |
| V | = | = volume of Medium, 900 mL |
Tolerances:
NLT 70% (Q) of the labeled amount of levetiracetam (C8H14N2O2) in 15 min for Tablets labeled to contain 250, or 500, or 750 mg; NLT 80% (Q) of the labeled amount of levetiracetam (C8H14N2O2) in 30 min for Tablets labeled to contain 1000 mg
Test 2:
If the product complies with this test, the labeling indicates that the product meets USP Dissolution Test 2.
Medium:
Water; 900 mL, deaerate, if necessary
Apparatus 2:
50 rpm
Time:
15 min
Buffer:
1.36 g/L of monobasic potassium phosphate, adjusted with 10% potassium hydroxide to a pH of 5.0
Mobile phase:
Acetonitrile and Buffer (10:90)
Standard solution:
54 µg/mL of USP Levetiracetam RS in Medium
Sample solution:
Pass a portion of the solution under test through a suitable filter. Dilute an aliquot with Medium to obtain a concentration similar to that of the Standard solution.
Chromatographic system
Mode:
LC
Detector:
UV 210 nm
Column:
4.6-mm × 15-cm; 5-µm packing L1
Column temperature:
30
Flow rate:
1.5 mL/min
Injection size:
20 µL
System suitability
Sample:
Standard solution
Suitability requirements
Tailing factor:
NMT 1.5
Relative standard deviation:
NMT 1.0%
Analysis
Samples:
Standard solution and Sample solution
Determine the percentage of levetiracetam (C8H14N2O2) dissolved:
Result = (rU/rS) × (CS/L) × D × V × 100
| rU | = | = peak response from the Sample solution |
| rS | = | = peak response from the Standard solution |
| CS | = | = concentration of USP Levetiracetam RS in the Standard solution (mg/mL) |
| L | = | = label claim (mg/Tablet) |
| D | = | = dilution factor of the Sample solution |
| V | = | = volume of Medium, 900 mL |
Tolerances:
NLT 80% (Q) of the labeled amount of levetiracetam (C8H14N2O2) is dissolved.
Test 3:
If the product complies with this test, the labeling indicates that the product meets USP Dissolution Test 3.
Medium:
Water; 900 mL
Apparatus 2:
50 rpm
Time:
30 min
Buffer, Mobile phase, Standard solution, Sample solution, Chromatographic system, System suitability, and Analysis:
Proceed as directed for Test 1.
Tolerances:
NLT 80% (Q) of the labeled amount of levetiracetam (C8H14N2O2) is dissolved.(RB 1-May-2011)
(RB 1-May-2011)
• Uniformity of Dosage Units 905:
Meet the requirements
905:
Meet the requirements
IMPURITIES
• Organic Impurities
Buffer:
6.8 g/L of monobasic potassium phosphate and 0.85 g/L of sodium 1-heptanesulfonate, adjusted with phosphoric acid to a pH of 2.8
Mobile phase:
Acetonitrile and Buffer (5:95)
System suitability solution:
3.6 µg/mL of USP Levetiracetam RS and 3.6 µg/mL of USP Levetiracetam Related Compound B RS in Mobile phase
Standard solution:
3.6 µg/mL of USP Levetiracetam RS in Mobile phase
Sample solution:
Equivalent to 1.2 mg/mL of levetiracetam from NLT 20 Tablets, finely crushed, in Mobile phase. [Note—Sonicate if necessary, and centrifuge the solution before passing through a suitable filter. ]
Chromatographic system
Mode:
LC
Detector:
UV 200 nm
Column:
4.6-mm × 25-cm; 4-µm packing L1
Flow rate:
1 mL/min
Injection size:
10 µL
System suitability
Samples:
System suitability solution and Standard solution
Suitability requirements
Resolution:
NLT 2.0 between levetiracetam related compound B and levetiracetam, System suitability solution
Tailing factor:
NMT 2.0, Standard solution
Relative standard deviation:
NMT 10.0%, Standard solution
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of each impurity in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × (1/F) ×100
| rU | = | = peak response of each impurity from the Sample solution |
| rS | = | = peak response of levetiracetam from the Standard solution |
| CS | = | = concentration of USP Levetiracetam RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of levetiracetam in the Sample solution (mg/mL) |
| F | = | = relative response factor (see Table 2) |
Acceptance criteria:
See Table 2.
Table 2
| Name | Relative Retention Time |
Relative Response Factor |
Acceptance Criteria, NMT (%) |
|---|---|---|---|
| Levetiracetam related compound Ba,b | 0.54 | — | — |
| Levetiracetam | 1.0 | — | — |
| Levetiracetam related compound Aa,c | 1.7 | — | — |
| Levetiracetam acidd | 2.1 | 0.79 | 0.3 |
| Any individual unspecified impurity | — | 1.0 | 0.1 |
| Total impurities | — | — | 0.6 |
|
a
These impurities are listed for information only; they are process impurities, which are controlled in the drug substance.
b
(S)-2-Aminobutanamide.
c
(S)-N-(1-Amino-1-oxobutan-2-yl)-4-chlorobutanamide.
d
(S)-2-(2-Oxopyrrolidine-1-yl)butanoic acid.
|
|||
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in tight containers. Store at controlled room temperature.
Add the following:
• Labeling:
When more than one Dissolution test is given, the labeling states the Dissolution test used only if Test 1 is not used.(RB 1-May-2011)
• USP Reference Standards 11
11
USP Levetiracetam RS 
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USP Levetiracetam Related Compound B RS
(S)-2-Aminobutanamide.
C4H10N2O 102.13
(S)-2-Aminobutanamide.
C4H10N2O 102.13
Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
| Topic/Question | Contact | Expert Committee |
|---|---|---|
| Monograph | Hariram Ramanathan, M.S.
Associate Scientific Liaison 1-301-816-8313 |
(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 3660
Pharmacopeial Forum: Volume No. 36(1) Page 115