Identification, Isolation, and Characterization of a New Degradation Impurity in Nafcillin Sodium

Abstract

A new degradant of Nafcillin Sodium was found at a level of 1.8% w/w during the gradient reversed-phase HPLC analysis in stability storage samples. This impurity was identified by LC-MS and was characterized by 1H-NMR, 13C-NMR, LC/MS/MS, elemental analysis, and IR techniques. Based on the structural elucidation data, this impurity was named as N-[(2S)-2-carboxy-2-{[(2-ethoxynaphthalen-1-yl)carbonyl]amino}ethylidene]-3-({N-[(2-ethoxynaphthalen-1-yl)carbonyl]glycyl}sulfanyl)-D-valine. This impurity was prepared by isolation and was co-injected into the HPLC system to confirm the retention time. To the best of our knowledge, this impurity has not been reported elsewhere. The identification and structural elucidation of this degradant impurity has been discussed in detail.

Isolation and structural characterization of novel thermal degradation impurity of nafcillin sodium using spectroscopic and computational techniques

“…This contrasts with the standard chemical shift range of ~145-160 ppm for CH=N sp 2 carbon (165.18 calculated, Table S1). 10 Taken collectively all the statistical correlations, the given experimental 1 H and 13 C NMR chemical shifts support to the proposed chemical structure of TDI.…”

“…Although this impurity is formed at 1.31 RRT which is very close to the impurity reported by Prasad et. al at 1.26 RRT having the chemical structure TDI-1 10 as shown in Figure 3, the structure proposed here is entirely different. The major difference between these two structures is that TDI has a thiazolidine ring whereas TDI-1 has an open chain structure.…”

“…has reported a new degradation impurity under thermal and humidity condition. 10 In the present study, NS subjected to degradation under thermal conditions. The HPLC chromatogram of NS showed the formation of an unknown impurity along with four known impurities at the relative retention time (RRT) of around 1.31 with respect to NS peak.…”