TY - JOUR
T1 - Identification of Novel Impurity of Ziprasidone
AU - Murkute, Sunil R.
AU - Singh, Girij P.
AU - Vasantharaju, S. G.
AU - Bhat, Krishnamurthy
AU - Godbole, Himanshu M.
AU - Upadhyay, Pritesh R.
AU - Trivedi, Anurag
N1 - Funding Information:
The authors are grateful to Lupin Research Park and Manipal Academy of Higher Education for allowing them to conduct this research. SRM is thankful to Lupin Research Park, R& D, Analytical team, Lupin Research Park for supporting the analyses. The authors report no declarations of interest.
Publisher Copyright:
© 2021 Elsevier B.V.
PY - 2022/1/5
Y1 - 2022/1/5
N2 - Ziprasidone hydrochloride is a second-generation antipsychotic drug employed for the treatment of schizophrenia and acute mania or mixed episodes associated with bipolar disorder. During the scale-up of ziprasidone hydrochloride, an unknown impurity was observed in the batches ranging from 0.10% to 0.15% by HPLC-UV analysis. The structure of an unknown impurity was proposed as 3,3′-methylenebis(5-(2-(4-(benzo[d]isothiazol-3-yl)piperazin-1-yl)ethyl)−6-chloroindolin-2-one) which is named as methylene ziprasidone dimer (MZD impurity). It was isolated from an enriched sample by preparative HPLC, and its structure was elucidated by comprehensive analysis of HRMS, 1D NMR (1H, 13C), DEPT-135, 2D NMR (COSY, HSQC, HMBC) spectroscopy. A plausible mechanism for the formation of isolated impurity is proposed.
AB - Ziprasidone hydrochloride is a second-generation antipsychotic drug employed for the treatment of schizophrenia and acute mania or mixed episodes associated with bipolar disorder. During the scale-up of ziprasidone hydrochloride, an unknown impurity was observed in the batches ranging from 0.10% to 0.15% by HPLC-UV analysis. The structure of an unknown impurity was proposed as 3,3′-methylenebis(5-(2-(4-(benzo[d]isothiazol-3-yl)piperazin-1-yl)ethyl)−6-chloroindolin-2-one) which is named as methylene ziprasidone dimer (MZD impurity). It was isolated from an enriched sample by preparative HPLC, and its structure was elucidated by comprehensive analysis of HRMS, 1D NMR (1H, 13C), DEPT-135, 2D NMR (COSY, HSQC, HMBC) spectroscopy. A plausible mechanism for the formation of isolated impurity is proposed.
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U2 - 10.1016/j.jpba.2021.114416
DO - 10.1016/j.jpba.2021.114416
M3 - Article
AN - SCOPUS:85117265815
SN - 0731-7085
VL - 207
JO - Journal of Pharmaceutical and Biomedical Analysis
JF - Journal of Pharmaceutical and Biomedical Analysis
M1 - 114416
ER -