Development and Validation of Stability Indicating RP HPLC method for the estimation of armodafinil and Characterization of its base Degradation Product by LC-MS/MS

Krishna Veni Nagappan, Neha Sungroya, Dakshayini Devi, Karthik Yamjala, Gowramma Byaran, Dhanabal S P


The present work focuses on the development and validation of a rapid, selective and reliable stability indicating reverse phase High Performance Liquid Chromatographic method for the quantitative analysis of Armodafinil (ARM). Armodafinil is a eugeroics drug used for treatment of narcolepsy and shift work sleep disorder and also as an adjunctive treatment for obstructive sleep apnea. The separation was carried out on a Hibar Purospher C18 (250 mm × 4.6 mm; 5μ) column by using 0.01 M ammonium formate (pH 4.5, Adjusted with acetic acid) and methanol as mobile phase in the ratio of 45:55 % v/v. The flow rate was maintained at 1 mL/min and the eluents were monitored at 220 nm. Stress studies were carried out with 1 mg/mL of the drug solution, starting with mild conditions and followed by intrinsic conditions to achieve sufficient degradation. Armodafinil underwent extensive degradation under basic hydrolysis condition. The unknown degradation product formed (DP I; 6.59±0.2 min) under the basic degradation condition was separated on a semi preparative HPLC, characterized by UPLC-Q-TOF and its fragmentation pathway was proposed. The proposed structure of the degradation product was confirmed by HRMS analysis. The developed stability indicating LC method was validated with respect to accuracy, precision, specificity/selectivity and linearity. The degradation product was characterized and reported.


Armodafinil; LC-MS/MS; degradation; Validation.

Full Text:




Tejaswi Jonnalagadda and Shanakumari Katakam, “A simple visible

spectrophotometric method for the determination of armodafinil in bulk

and pharmaceutical dosage form”, Int. J. Pharm Sci Res. vol. 6(6), pp.

-2581, June 2015.

P. Vivek Sagar, Nelofer Bagum, and S. Shobha Rani, “Stability

indicating RP HPLC method for the estimation armodafinil in tablet

dosage form”, Int. J. Pharm. Pharma Sci. vol. 6, pp. 604-609, September

Ramesh Devi, Ramakrishna Singirikonda, and Haiduddin Mohammad,

“Development and validation of LC-MS/Ms method for the

determination of armodafinil in human plasma”, Current Pharm Anal.

vol. 8, pp. 295-305, September 2012.

Mamta P. Devadiga, P. Anandan, and Arindam Mukhopadhyay,

“Development of a rapid and sensitive method for estimation of

armodafinil in human plasma by LC MS/MS”, Int. J. App Bio Pharm

Tech. vol. 2, pp. 323-337, MarcPhah 2011.

L. Jennifer Donovan, J.Robert Malcolm, S. John Markowitz, and C.

Lindsay Devane, “Chiral analysis of d- and l-modafinil in human

serum: application of human pharmacokinetic studies”, Ther. Drug

Monitor. vol. 25, pp. 197-202, April 2003.

Khaldun M. AL Azzam, Bahruddin Saad, Rohana Adnan, and

Muhammad Idiris Saleh, “Enantioselective determination of modafinil

in pharmaceutical formulations by capillary electrophoresis, and

computational calculation of their inclusion complexes”, Micro Chim

Acta. vol. 166, pp.311-317, September 2009.

R. Nageswara Rao, Dhananjay D. Shinde, and M.V.N. Kumar Talluri,

“Development and validation of a reverse phase liquid chromatographic

method for separataion and determination of related substancces of

modafinil in bulk drugs”. Talanta. vol. 73, pp. 407-414, September 2007.

Ramisetti Nageswara rao, Dhananjay D. Shinde, and Murali V.N.

Kumar Talluri, “Enantioselective HPLC resolution of synthetic

intermediates of armodafinil and related substances”, J. Sep. Sci. vol. 31,

pp. 981-989, April 2008.

Wei Wang, Suyun Xiang, Xiaojuan Zhou, Yibing Ji, and Bingren Xiang,

“Enantiomeric impurity and determination of the enantiomeric impurity

of armodafinil by capillary electrophoresis with sulfobutyl ether β

cyclodextrin”, molecules. vol. 17, pp. 303-314, January 2012.

Mona Darwish, Mary Bond, Edward T. Hellriegel, James M. Youakim,

Ronghua Yang, and Philmore Robertson Jr, “Investigation of a possible

interaction betwee quetiapine and armodafinil in patients with

schizophrenia an open label, multiple dose study”, J. Clin Pharmacol.

vol. 52, pp. 1399-1409, September 2012.

Deepti Jain and Pawan Basniwal, “Intrinsic stability of armodafinil

hydrochloride by forced degradation and impurity profiling”,

Pharmaceutica Analytica Acta. vol.7, pp. 1-18, February 2016.

ICH, Q1A. Stability Testing of New Drug Substances and Products.

International Conference on Harmonization, IFPMA, Geneva, 1993.

ICH, Q2A. Text on validation of analytical procedures, International

Conference on Harmonization, October 1994.


  • There are currently no refbacks.

Copyright (c) 2017 GSTF Journal of Advances in Medical Research (JAMR)