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Add the following:

Add the following: Levetiracetam Tablets DEFINITION Levetiracetam Tablets contain NLT 90.0% and NMT 110.0% of the

Levetiracetam Tablets

DEFINITION

Levetiracetam Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of levetiracetam

(C 8 H 14 N 2 O 2 ).

IDENTIFICATION

• A. INFRARED ABSORPTION

• B. The retention time of the major peak of the Sample solution corresponds to that of the Standard

197K

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 (2:23)

Diluent: Acetonitrile and water (1:4)

Standard solution: 0.35 mg/mL of USP Levetiracetam RS in Diluent. [NOTE—Sonicate if

necessary to dissolve. ]

Sample solution: Nominally equivalent to 0.4 mg/mL of levetiracetam in Diluent from NLT 20

Tablets, finely crushed. [NOTE—Sonicate if necessary to dissolve. ]

Chromatographic system

(See

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

-µm packing L1 Flow rate: 2 mL/min Injection size: 10 µL Chromatography 621 , System Suitability

Chromatography

621

, System Suitability.)

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 C 8 H 14 N 2 O 2 in the portion of Tablets taken:

r

r

U

S

C S

Result = (r U /r S ) × (C S /C U ) × 100

=

peak response from the Sample solution

=

peak response from the Standard solution

=

concentration of USP Levetiracetam RS in the Standard solution (mg/mL)

=

nominal concentration of levetiracetam in

C U

e Sample solution (mg/mL)

Acceptance criteria: 90.0%–110.0%

PERFORMANCE TESTS

DISSOLUTION

90.0%–110.0% PERFORMANCE TESTS • D ISSOLUTION 711 Medium: Water, 900 mL Apparatus 2: 50 rpm Time:

711

Medium: Water, 900 mL

Apparatus 2: 50 rpm

Time:

See Table 1 below.

Table 1

Tablet Strength Time (mg/Tablet) (min) 250 15 500 15 750 15 1000 30
Tablet Strength Time
(mg/Tablet)
(min)
250
15
500
15
750
15
1000
30

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 (3:17)

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 0.45-µm filter.

Chromatographic system

(See Chromatography

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

621

, System Suitability.)

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 amount of C 8 H 14 N 2 O 2 dissolved:

Result = (r U /r S ) × (C S /L) × V × 100

r

r

U

S

C S

L

=

peak response from the Sample solution

=

peak response from the Standard solution

=

concentration of USP Levetiracetam RS in the Standard solution (mg/mL)

=

label claim (mg/Tablet)

Tolerances: NLT 70% (Q) of the labeled amount of C 8 H 14 N 2 O 2 in 15 min for Tablets labeled to

contain 250 mg, or 500 mg, or 750 mg; NLT 80% (Q) of the labeled amount of C 8 H 14 N 2 O 2 in 30

min for Tablets labeled to contain 1000 mg

: Meet the requirements

UNIFORMITY OF DOSAGE UNITS

905

the requirements • U NIFORMITY OF D OSAGE U NITS 905 IMPURITIES Organic Impurities • P

IMPURITIES

Organic Impurities

• PROCEDURE

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 (1:19)

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 USP Levetiracetam RS in Mobile phase

Sample solution: Equivalent to 1.2 mg/mL of levetiracetam in Mobile phase from NLT 20 Tablets

finely crushed. [NOTE—Sonicate if necessary, and centrifuge the solution before passing through

a suitable filter. ]

Chromatographic system

(See

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

-µm packing L1 Flow rate: 1 mL/min Injection size: 10 µL Chromatography 621 , System Suitability

Chromatography

621

, System Suitability.)

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 = (r U /r S ) × (C S /C U ) × (1/F) ×100

r

U

r

S

C

S

C

U

F

=

peak response of each impurity from the

=

Sample solution peak response of levetiracetam from the

=

Standard solution concentration of USP Levetiracetam RS in

=

the Standard solution (mg/mL) nominal concentration of levetiracetam in the Sample solution (mg/mL)

=

relative response factor as listed in Impurity

able 1

Acceptance criteria

Individual impurities: See Impurity Table 1.

Total impurities: NMT 0.6%

Impurity Table 1 Relative Relative Acceptance Retention Response Criteria, Name Time Factor NMT (%) a,b
Impurity Table 1
Relative
Relative
Acceptance
Retention
Response
Criteria,
Name
Time
Factor
NMT (%)
a,b
Levetiracetam related compound B
Levetiracetam
0.54
1.0
a,c
Levetiracetam related compound A
1.7
d
Levetiracetam acid
Any individual unspecified impurity
2.1
0.79
0.3
1.0
0.1
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.

USP REFERENCE STANDARDS USP LEVETIRACETAM RS

11

USP LEVETIRACETAM RELATED COMPOUND B RS

[(S)-2-aminobutanamide]

R ELATED C OMPOUND B RS [( S )-2-aminobutanamide] USP34 ( C 4 H 10 N

USP34

(C 4 H 10 N 2 O

102.13).

USP34 ( C 4 H 10 N 2 O 102.13). Auxiliary Information— Please check for your

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 (SM42010)
Topic/Question
Contact
Expert Committee
Monograph
Ravi Ravichandran, Ph.D.
Principal Scientific Liaison
(SM42010) Monographs - Small Molecules 4
1-301-816-8330
711
Margareth R.C. Marques,
Ph.D.
Senior Scientific Liaison
(GCDF2010) General Chapters - Dosage
Forms
1-301-816-8106
Reference
RS Technical Services
Standards
1-301-816-8129
rstech@usp.org

USP34–NF29 Page 3287 Pharmacopeial Forum: Volume No. 36(1) Page 115 Chromatographic Column— LEVETIRACETAM TABLETS

Chromatographic columns text is not derived from, and not part of, USP 34 or NF 29.