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STRUCTURE DETERMINATION OF IMPURITY IN MEMANTINE
HYDROCHLORIDE BY ANALYTICAL TECHNIQUES
MUKESH KUMAR GUPTA
1
& MANOHAR V. LOKHANDE
2
1
Department of Chemistry, Shri Jagdish Prasad Jhabarmal Tibrewala University,
Vidya Nagari, Jhunjhunu, Chudela, Rajasthan, India
1
IPCA Laboratories Ltd, Chemical Research Division, Kandivli Industrial Estate,
Kandivli (W), Mumbai, Maharashtra, India
2
Department of Chemistry, Sathaye College, Vileparle (E), Mumbai, Maharashtra, India
ABSTRACT
Impurity related to the synthesis of pharmaceutical ingredient Memantine hydrochloride bulk drug was detected
by GC and was subjected to GCMS for identification. The proposed impurity was prepared synthetically and was injected
on GC for comparison of retention time with that of the unknown impurity in Memantine. The GCMS spectra of
synthetically made impurity and that of process related impurity in the Memantine hydrochloride were found to be the
similar. The postulated structure was unambiguously confirmed with the help of NMR and IR analysis. Based on GCMS,
NMR and IR data the structure of the impurity was proposed to be 1,3-diacetamido-5,7-dimethyl Tricyclo decane
(Diacetamido impurity). This impurity which was elucidated was not found to be previously reported in any synthetic or
analytical literature pertaining to Memantine hydrochloride.
KEYWORDS: Memantine Hydrochloride, Impurity, GC, GCMS, NMR, IR Structural Elucidation
INTRODUCTION
Memantine hydrochloride, designated as 1-amino-3, 5 dimethyl- adamantane hydrochloride, belongs to a small
group of drugs known as Tricyclic Antivirals (TAVs), and provide good and persistent activation of central nervous system
N-methyl-d-aspartate (NMDA) receptors, and hence can be used in the treatment of Parkinson’s and Alzheimer’s
diseases[1].
We have screened the literatures for impurities which were produced from different synthetic processes and have
found that this unknown impurity was not reported in any of the synthetic processes related to Memantine. Methods based
on GC, GCMS, NMR, IR related to impurities were studied in the present article. However, so far there is no published
report, describing the complete characterisation of this unknown process related impurity in Memantine hydrochloride
active pharmaceutical ingredient (API).
The impurity profile of the drug substance is critical for its safety assessment and manufacturing process. It is
mandatory to identify and characterize the impurities in a pharmaceutical product, if present above the accepted limit of
0.10% [2]. 3’ carbon of adamantane derivative undergoes conversion to form the 1-acetamido-3,5-dimethyl tricyclo decane
(AC-NHDMAD) [3]. There are few methods which are reported for synthesis of AC-NHDMAD, which is an intermediate
used in the synthesis of Memantine hydrochloride. These methods are very facile, safe and can be easily scaleable [1].
International Journal of General Medicine
and Pharmacy (IJGMP)
ISSN(P): 2319-3999; ISSN(E): 2319-4006
Vol. 3, Issue 4, July 2014, 75-84
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