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.
The current study dealt with the degradation behavior of lacosamide (LAC) under ICH prescribed stress conditions. LAC was found to be labile under acid and base hydrolytic stress conditions, while it was stable to neutral hydrolytic, oxidative, photolytic and thermal stress. In total, seven degradation products (DPs) were formed, which were separated on a C18 column using a stability-indicating method. LC-MS analyses indicated that one of the DPs had the same molecular mass as that of the drug. Structural characterization of DPs was carried out using ESI-Q-TOF-MS/MS technique. The degradation pathways and mechanisms of degradation of the drug were delineated by carrying out the degradation in different co-solvents viz. methanol, deuterated methanol, ethanol, 1-propanol and acetonitrile. The developed LC method was validated for the determination of related substances and assay of LAC as per ICH guidelines. This study demonstrates a comprehensive approach of LAC degradation studies during its development phase.
HPLC Group, Analytical Chemistry Division, IICT, Tarnaka, Hyderabad 500007, India. Electronic address: rnrao55@yahoo.com.
Nageswara Rao
NR
Ramisetti
HPLC Group, Analytical Chemistry Division, IICT, Tarnaka, Hyderabad 500007, India.
Ramakrishna
R
Kuntamukkala
National Centre for Mass Spectrometry, IICT, Tarnaka, Hyderabad 500007, India.
Sridhar
S
Lakshetti
National Centre for Mass Spectrometry, IICT, Tarnaka, Hyderabad 500007, India.
Prabhakar
P
Sripadi
D000081:Acetamides / Q000032:analysis* / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004355:Drug Stability; D000078334:Lacosamide; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods*
D000081:Acetamides; D000078334:Lacosamide
ESI-MS/MS; Forced degradation; Lacosamide; RP-HPLC; Stability indicating