Identification and characterization of stress degradants of lacosamide by LC–MS and ESI-Q-TOF-MS/MS: Development and validation of a stability indicating RP-HPLC method

Ramisetti, Nageswara Rao; Kuntamukkala, Ramakrishna; Lakshetti, Sridhar; Prabhakar, S.

doi:10.1016/j.jpba.2014.03.010

Cited by 14 publications

(9 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In comparison to acidic stress condition (Figure 2-B), one different degradation product, compound 3, was observed under the alkaline stress condition (Table 2, Figure 2-C). In this study, lacosamide showed an extensive degradation under the oxidative stress conditions ( Figure 2-D), which are different from what is reported in the literature [15]. The results of this study suggest that lacosamide was unstable under the acidic, alkaline, and oxidative stress conditions, and should be stored in a tightly sealed container, protected from oxidizing agents.…”

Section: Methodscontrasting

confidence: 97%

“…Identification of Degradation Products from Prior Literature. Based on the mass spectra of the degradation products and the data reported in the literature [13][14][15] Figure 4.…”

Section: Methodsmentioning

confidence: 99%

“…A few high-performance liquid chromatography (HPLC) and liquid chromatography-mass spectrometry (LC-MS) methods for studying degradation products and impurities in lacosamide have been reported [13][14][15][16][17][18][19]. Among them, three literature studies have been reported for the characterization of forced degradation products.…”

Section: Introductionmentioning

confidence: 99%

“…Apexa et al [14] characterized 3 degradation products of lacosamide. In addition, Ramisetti et al [15] studied the degradation behavior of lacosamide under the International Conference on Harmonisation (ICH)-prescribed stress conditions and characterized 6 degradation products using electrospray-ionization quadrupole time-of-flight tandem mass spectrometry (ESI-Q-TOF-MS/MS) technique. However, during our preliminary experiment, lacosamide underwent extensive degradation in acidic, alkaline, and oxidative degradation, which was different from what reported in the literature [15].…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Identification of forced degradation products of lacosamide by LC-QQLIT-MS and LC-IT/TOF-MS

Zhou

et al. 2019

Acta Chromatographica

View full text Add to dashboard Cite

Lacosamide, a new type of antiepileptic drug, was subjected to forced degradation under the conditions of hydrolysis (acidic and alkaline), oxidation, dry heat, and photolysis to characterize its possible degradation products. The drug showed significant degradation under acidic, alkaline and oxidative conditions. The degradation products were separated on an Agilent Zorbax SB-C 18 column with gradient elution using a mobile phase consisting of acetonitrile and ammonium acetate (0.002 mol/L) with formic acid as additive. A combination of liquid chromatography hybrid triple quadrupole-linear ion trap mass spectrometry (LC-QqLIT-MS) and liquid chromatography hybrid ion trap/time-of-flight mass spectrometry (LC-IT/TOF-MS) was used to identify degradation products. A total of 7 products including 4 novel degradation products were characterized. The mechanisms of degradation products of lacosamide were discussed. Application of the method to study degradation products of lacosamide provided fragment information, allowing further investigation of the degradation pathways and intrinsic stability of the drug.

show abstract

Section: Methodscontrasting

confidence: 97%

“…Identification of Degradation Products from Prior Literature. Based on the mass spectra of the degradation products and the data reported in the literature [13][14][15] Figure 4.…”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Identification of forced degradation products of lacosamide by LC-QQLIT-MS and LC-IT/TOF-MS

Zhou

et al. 2019

Acta Chromatographica

View full text Add to dashboard Cite

show abstract

“…All published methods for the determination of lacosamide in biological samples use LC . To our knowledge, there is no validated method in the literature for the determination of lacosamide using GC–MS.…”

Section: Introductionmentioning

confidence: 99%

A fully validated method for the determination of lacosamide in human plasma using gas chromatography with mass spectrometry: Application for therapeutic drug monitoring

Νικολάου

Papoutsis

Spiliopoulou

et al. 2014

J of Separation Science

View full text Add to dashboard Cite

A simple gas chromatographic method with mass spectrometry detection was developed and validated for the determination of lacosamide in human plasma. Lacosamide and the internal standard, levetiracetam-d6, were extracted from 200 μL plasma, by a solid-phase extraction through HF Bond Elut C18 columns, and derivatized using N-methyl-N-tert-butyldimethylsilyltrifluoroacetamide with 1% tert-butyldimethylsilylchloride in acetonitrile. The limit of quantification was found to be 0.20 μg/mL and the assay was linear up to 20.0 μg/mL with correlation coefficient ≥0.994. The intra- and interday precision values were <4.1% in terms of relative standard deviation (%) and the values of intra- and interday accuracy were found to be within -7.2 and 5.3% in terms of relative error (%). Absolute recovery of the method for lacosamide was determined at three concentration levels and ranged from 92.5 to 97.6%. The developed method uses small volumes of plasma and proved to be simple, rapid, and sensitive for the determination of lacosamide in plasma. This method can be used in routine every day analysis of plasma samples obtained from patients who follow respective antiepileptic treatment and for the investigation of clinical and forensic cases where lacosamide is involved.

show abstract

Highly sensitive UHPLC–DAD method for simultaneous determination of two synergistically acting antiepileptic drugs; levetiracetam and lacosamide: Application to pharmaceutical tablets and human urine

Mohamed

Ali

Rageh

et al. 2019

Biomedical Chromatography

View full text Add to dashboard Cite

A simple and highly sensitive ultra‐high‐performance liquid chromatographic–diode array (UHPLC‐DAD) detection method was developed and validated for the simultaneous estimation of levetiracetam (LEV) and lacosamide (LAC). It was clinically proven that the combination of LEV and LAC exhibits a synergistic effect against refractory seizures in mice, which was the motivation for the analysis of this binary mixture both in bulk and in human urine samples. The binary mixture was resolved on a Hypersil BDS C18 analytical column, utilizing a mobile phase of 0.050 mol L−1 phosphate buffer (pH 5.60), methanol and acetonitrile in the ratio (80:10:10 v/v/v) using catechol as an internal standard. The mobile phase was pumped at a flow rate of 1.2 mL min−1 with diode array detection at 205 nm for both drugs and 270 nm for IS. Calibration curves were linear with correlation coefficient >0.9990 over the studied concentration range of 0.1–70.0 μg mL−1 for both drugs. The developed method was reproducible with low relative standard deviation values for intra‐ and inter‐day precision (<2.0%). Both drugs were determined in bulk, pharmaceutical formulations and human urine samples without any interference from complex matrices.

show abstract

Identification and characterization of stress degradants of lacosamide by LC–MS and ESI-Q-TOF-MS/MS: Development and validation of a stability indicating RP-HPLC method

Cited by 14 publications

References 11 publications

Identification of forced degradation products of lacosamide by LC-QQLIT-MS and LC-IT/TOF-MS

Identification of forced degradation products of lacosamide by LC-QQLIT-MS and LC-IT/TOF-MS

A fully validated method for the determination of lacosamide in human plasma using gas chromatography with mass spectrometry: Application for therapeutic drug monitoring

Highly sensitive UHPLC–DAD method for simultaneous determination of two synergistically acting antiepileptic drugs; levetiracetam and lacosamide: Application to pharmaceutical tablets and human urine

Contact Info

Product

Resources

About