EUROPEAN PHARMACOPOEIA 11.

0 Lacosamide oral solution

IDENTIFICATION System suitability : reference solution (a) :

A. Record the UV spectrum of the principal peak in the – repeatability : maximum relative standard deviation of
chromatograms obtained with the solutions used in 1.5 per cent determined on 6 injections.
the assay with a diode array detector in the range of Calculate the percentage content of lacosamide (C13H18N2O3)
210-400 nm. taking into account the assigned content of lacosamide CRS.
Results : the UV spectrum of the principal peak in
the chromatogram obtained with the test solution is IMPURITIES
similar to the UV spectrum of the principal peak in the Specified impurities : D.
chromatogram obtained with reference solution (a). Other detectable impurities (the following substances would, if
B. Examine the chromatograms obtained in the assay. present at a sufficient level, be detected by one or other of the
Results : the principal peak in the chromatogram obtained tests in the monograph) : B, C, E, F, J, K.
with the test solution is similar in retention time and size
to the principal peak in the chromatogram obtained with
reference solution (a).
TESTS
Related substances. Liquid chromatography (2.2.29).
Solvent mixture : acetonitrile R, water R (13:87 V/V).
Test solution. Mix the contents of 10 vials of the preparation to B. (2Ξ)-2-acetamido-3-(benzylamino)-3-oxopropyl acetate,
be examined and dilute a suitable volume of the solution with
the solvent mixture to obtain a concentration of lacosamide
of 1.0 mg/mL.
Reference solution (a). Dissolve 20.0 mg of lacosamide CRS
in the solvent mixture and dilute to 20.0 mL with the solvent
mixture. C. (2Ξ)-N-benzyl-3-methoxy-2-(N-methylacetamido)-
Reference solution (b). Dilute 1.0 mL of the test solution to propanamide,
100.0 mL with the solvent mixture. Dilute 2.0 mL of this
solution to 10.0 mL with the solvent mixture.
Reference solution (c). Dissolve 2 mg of lacosamide
impurity D CRS and 3 mg of lacosamide impurity F CRS in the
solvent mixture and dilute to 100 mL with the solvent mixture.
Dilute 1 mL of the solution to 10 mL with the solvent mixture. D. (2Ξ)-2-amino-N-benzyl-3-methoxypropanamide,
Column :
– size : l = 0.15 m, Ø = 4.6 mm ;
– stationary phase : end-capped extra-dense bonded octylsilyl
silica gel for chromatography R (5 μm) ;
– temperature : 35 °C.
E. (2Ξ)-2-amino-N-benzyl-3-hydroxypropanamide,
Mobile phase : methanesulfonic acid R, acetonitrile R1, water
for chromatography R (0.75:130:870 V/V/V).
Flow rate : 2.0 mL/min.
Detection : spectrophotometer at 215 nm.
Injection : 5 μL of the test solution and reference solutions (b)
and (c). F. (2Ξ)-2-acetamido-N-benzyl-3-hydroxypropanamide,
Run time : 2.5 times the retention time of lacosamide.
Identification of impurities : use the chromatogram obtained
with reference solution (c) to identify the peaks due to
impurities D and F.
Relative retention with reference to lacosamide J. phenylmethanamine,
(retention time = about 6 min) : impurity D = about 0.4 ;
impurity F = about 0.5.
System suitability : reference solution (c) :
– resolution : minimum 1.5 between the peaks due to
impurities D and F. K. 2-acetamido-N-benzylprop-2-enamide.
Calculation of percentage contents :
– for each impurity, use the concentration of lacosamide in 01/2021:2990
reference solution (b).
Limits :
– impurity D : maximum 0.8 per cent ;
– unspecified impurities : for each impurity, maximum 0.2 per
cent ; LACOSAMIDE ORAL SOLUTION
– total : maximum 2.0 per cent ;
– reporting threshold : 0.1 per cent. Lacosamidi solutio peroralis
ASSAY DEFINITION
Liquid chromatography (2.2.29) as described in the test for Oral solution of Lacosamide (2992), for human use.
related substances with the following modifications. It complies with the monograph Liquid preparations for oral
Injection : test solution and reference solution (a). use (0672) and the following additional requirements.

General Notices (1) apply to all monographs and other texts 3187
www.webofpharma.com
Lacosamide oral solution EUROPEAN PHARMACOPOEIA 11.0

Content : 95.0 per cent to 105.0 per cent of the content of Calculation of percentage contents :
lacosamide (C13H18N2O3) stated on the label. – for each impurity, use the concentration of lacosamide in
reference solution (b).
IDENTIFICATION
Limits :
A. Record the UV spectrum of the principal peak in the
chromatograms obtained with the solutions used in – impurity D : maximum 0.6 per cent ;
the assay, with a diode array detector in the range of – unspecified impurities : for each impurity, maximum 0.2 per
210-400 nm. cent ;
Results : the UV spectrum of the principal peak in – total : maximum 2.0 per cent ;
the chromatogram obtained with the test solution is – reporting threshold : 0.1 per cent.
similar to the UV spectrum of the principal peak in the
chromatogram obtained with reference solution (a). ASSAY
B. Examine the chromatograms obtained in the assay. Liquid chromatography (2.2.29) as described in the test for
Results : the principal peak in the chromatogram obtained related substances with the following modifications.
with the test solution is similar in retention time and size Mobile phase :
to the principal peak in the chromatogram obtained with – mobile phase A : 0.05 per cent V/V solution of trifluoroacetic
reference solution (a). acid R ;
TESTS – mobile phase B : trifluoroacetic acid R, acetonitrile R1
(0.5:1000 V/V) ;
Related substances. Liquid chromatography (2.2.29).
Time Mobile phase A Mobile phase B
Solvent mixture : acetonitrile R, water R (13:87 V/V).
(min) (per cent V/V) (per cent V/V)
Test solution. Dilute a suitable volume of the preparation to be
0-9 75 25
examined with the solvent mixture to obtain a concentration
of lacosamide of 1.0 mg/mL. 9 - 12.5 45 55
Reference solution (a). Dissolve 20.0 mg of lacosamide CRS
in the solvent mixture and dilute to 20.0 mL with the solvent Injection : 4 μL of the test solution and reference solution (a).
mixture. System suitability : reference solution (a) :
Reference solution (b). Dilute 1.0 mL of the test solution to – repeatability : maximum relative standard deviation of
100.0 mL with the solvent mixture. Dilute 2.0 mL of this 1.5 per cent determined on 6 injections.
solution to 10.0 mL with the solvent mixture. Calculate the percentage content of lacosamide (C13H18N2O3)
Reference solution (c). Dissolve 2 mg of lacosamide taking into account the assigned content of lacosamide CRS.
impurity D CRS and 3 mg of lacosamide impurity F CRS in the
solvent mixture and dilute to 100 mL with the solvent mixture. IMPURITIES
Dilute 1 mL of the solution to 10 mL with the solvent mixture. Specified impurities : D.
Column : Other detectable impurities (the following substances would,
– size : l = 0.25 m, Ø = 4.6 mm ; if present at a sufficient level, be detected by one or other of
the tests in the monograph) : E, F, G, J, K.
– stationary phase : end-capped octadecylsilyl silica gel for
chromatography compatible with 100 per cent aqueous
mobile phases R (5 μm);
– temperature : 30 °C.
Mobile phase :
– mobile phase A : trifluoroacetic acid R, acetonitrile R1, water D. (2Ξ)-2-amino-N-benzyl-3-methoxypropanamide,
for chromatography R (0.56:100:900 V/V/V) ;
– mobile phase B : trifluoroacetic acid R, acetonitrile R1
(0.5:1000 V/V) ;
Time Mobile phase A Mobile phase B
(min) (per cent V/V) (per cent V/V)
0 - 31 100 0 E. (2Ξ)-2-amino-N-benzyl-3-hydroxypropanamide,
31 - 33 30 70

Flow rate : 1.5 mL/min.

Detection : spectrophotometer at 215 nm.
Injection : 5 μL of the test solution and reference solutions (b)
and (c). F. (2Ξ)-2-acetamido-N-benzyl-3-hydroxypropanamide,
Identification of impurities : use the chromatogram obtained
with reference solution (c) to identify the peaks due to
impurities D and F ; impurities D and F may be inverted in the
elution order, but the peak area of each impurity is different,
so a clear identification of the impurities is possible.
Relative retention with reference to lacosamide G. N-benzylacetamide,
(retention time = about 27 min) : impurity D = about 0.4 ;
impurity F = about 0.5 (D and F may be inverted).
System suitability : reference solution (c) :
– resolution : minimum 3.0 between the peaks due to
impurities D and F. J. phenylmethanamine,

3188 See the information section on general monographs (cover pages)

www.webofpharma.com
EUROPEAN PHARMACOPOEIA 11.0 Lacosamide tablets

Injection : 5 μL of the test solution and reference solutions (b)

and (c).
Run time : 2.5 times the retention time of lacosamide.
Identification of impurities: use the chromatogram obtained
K. 2-acetamido-N-benzylprop-2-enamide. with reference solution (c) to identify the peaks due to
impurities D and F.
01/2022:2989 Relative retention with reference to lacosamide
(retention time = about 6 min) : impurity D = about 0.4 ;
impurity F = about 0.5.
System suitability : reference solution (c) :
– resolution : minimum 1.5 between the peaks due to
impurities D and F.
LACOSAMIDE TABLETS Calculation of percentage contents :
– for each impurity, use the concentration of lacosamide in
Lacosamidi compressi reference solution (b).
DEFINITION Limits :
Tablets containing Lacosamide (2992), for human use. – unspecified impurities : for each impurity, maximum 0.2 per
They comply with the monograph Tablets (0478) and the cent ;
following additional requirements. – total : maximum 1.0 per cent ;
Content : 95.0 per cent to 105.0 per cent of the content of – reporting threshold : 0.1 per cent.
lacosamide (C13H18N2O3) stated on the label. Dissolution(1) (2.9.3, Apparatus 2).
IDENTIFICATION Dissolution medium : 10.3 g/L solution of hydrochloric acid R.
A. Record the UV spectrum of the principal peak in the Use 900 mL of the medium.
chromatograms obtained with the solutions used in Rotation speed : 50 r/min.
the assay, with a diode array detector in the range of Time : 30 min.
210-400 nm. Analysis. Liquid chromatography (2.2.29).
Results : the UV spectrum of the principal peak in Test solutions. Samples withdrawn from the dissolution
the chromatogram obtained with the test solution is vessel and filtered.
similar to the UV spectrum of the principal peak in the Reference solution. Using sonication, dissolve a suitable
chromatogram obtained with reference solution (a). quantity of lacosamide CRS in a suitable volume of
B. Examine the chromatograms obtained in the assay. the dissolution medium to obtain a concentration of
Results : the principal peak in the chromatogram obtained lacosamide corresponding to the theoretical concentration
with the test solution is similar in retention time and size of lacosamide in the test solution, based on the labelled
to the principal peak in the chromatogram obtained with content of the tablets.
reference solution (a). Column :
TESTS – size : l = 0.05 m, Ø = 4.6 mm ;
Related substances. Liquid chromatography (2.2.29). – stationary phase : end-capped octadecylsilyl silica gel for
chromatography R (3 μm) ;
Solvent mixture : acetonitrile R, water R (13:87 V/V).
– temperature : 35 °C.
Test solution. To 10 tablets add a suitable volume of the
solvent mixture to obtain a concentration of lacosamide of Mobile phase : trifluoroacetic acid R, acetonitrile R1, water
2-4 mg/mL. Shake vigorously for 30 min, sonicate for 10 min for chromatography R (1:300:700 V/V/V).
and allow to stand for 30 min. Dilute a suitable volume of the Flow rate : 1.0 mL/min.
supernatant with the solvent mixture to obtain a concentration Detection : spectrophotometer at 215 nm.
of lacosamide of 1.0 mg/mL. Injection : 2 μL.
Reference solution (a). Dissolve 20.0 mg of lacosamide CRS Run time : 2.5 min.
in the solvent mixture and dilute to 20.0 mL with the solvent System suitability : reference solution :
mixture.
– repeatability : maximum relative standard deviation of
Reference solution (b). Dilute 1.0 mL of the test solution to 1.5 per cent determined on 6 injections.
100.0 mL with the solvent mixture. Dilute 2.0 mL of this
solution to 10.0 mL with the solvent mixture. Calculate the amount of dissolved lacosamide (C13H18N2O3),
expressed as a percentage of the content stated on the label,
Reference solution (c). Dissolve 2 mg of lacosamide taking into account the assigned content of lacosamide CRS.
impurity D CRS and 3 mg of lacosamide impurity F CRS in the
solvent mixture and dilute to 100 mL with the solvent mixture. Acceptance criterion :
Dilute 1 mL of the solution to 10 mL with the solvent mixture. – Q = 80 per cent after 30 min.
Column : ASSAY
– size : l = 0.15 m, Ø = 4.6 mm ; Liquid chromatography (2.2.29) as described in the test for
– stationary phase : end-capped extra-dense bonded octylsilyl related substances with the following modifications.
silica gel for chromatography R (5 μm) ; Injection : test solution and reference solution (a).
– temperature : 35 °C. System suitability : reference solution (a) :
Mobile phase : methanesulfonic acid R, acetonitrile R1, water – repeatability : maximum relative standard deviation of
for chromatography R (0.75:130:870 V/V/V). 1.5 per cent determined on 6 injections.
Flow rate : 2.0 mL/min. Calculate the percentage content of lacosamide (C13H18N2O3)
Detection : spectrophotometer at 215 nm. taking into account the assigned content of lacosamide CRS.
(1) The test approved in the marketing authorisation is to be used for routine quality control to confirm batch-to-batch consistency. For more information please consult Ph. Eur.
1. General Notices.

General Notices (1) apply to all monographs and other texts 3189
www.webofpharma.com