An Improved Ion Chromatographic Method for Fast and Sensitive Determination of N-Methylpyrrolidine in Cefepime Hydrochloride

Abstract

An alternative ion chromatographic method to the existing USP method for the determination of N-methylpyrrolidine (NMP) in cefepime hydrochloride is developed. The cefepime in solution behaves as a strong cation and gets retained in the analytical column, leading to reduction in column capacity and irreproducible retention time. The retained drug has to be removed with a special rinsing solution, followed by re-equilibration with the mobile phase. This process takes at least 3 to 4 h time for sample analysis. We used a silica-based cation exchange column with poly-butadiene-maleic acid functional group attached with an optimized mobile phase composition. The characteristic feature of this method is the short analysis time with a clear separation of NMP and the cationic drug molecule within a run-time of 30 min. The developed method overcomes the limitations of the USP method. This method describes the matrix elimination by choosing appropriate column and eluent condition. The method is tested for selectivity, linearity, limits of detection and quantification, accuracy, and precision and is suitable for continuous sample analysis.

Analysis of N-methylpyrrolidine in cefepime hydrochloride by ion chromatography using suppressed conductivity detection with solid-phase extraction pre-treatment

“…10) and 28 min. 11 This ve-fold improvement in sample through-put, combined with the seven-fold improvement in stability, means that it is now possible to prepare a number of samples simultaneously for automated injection instead of being obliged to inject samples immediately aer preparation, as at present. 5 The use of a refrigerated autosampler would mean that sample solutions would be stable for a number of days.…”

“…The stability of cefepime (measured by the rate of formation of NMP) was evaluated over four days in deionised water at À17 C, 4 C and 25 C. An increase in NMP concentration from 0.23% to 0.27% was observed aer 1 h at 25 C. At 4 C, the NMP concentration changed from 0.22% to 0.29% over 24 h, but no signicant increase in NMP concentration was observed in frozen samples (À17 C) aer four days. Subramanian et al 11 suggested an improved ion chromatographic method designed to overcome the fouling of resin-based ion chromatography columns by cefepime. They used a silica-based cation exchange column with a mobile phase comprising 0.006 mol L À1 nitric acid with 10% acetonitrile.…”

Rapid determination of N-methylpyrrolidine in cefepime by combining direct infusion electrospray ionisation-time-of-flight mass spectrometry with field asymmetric waveform ion mobility spectrometry

“…At present, there are four main techniques employed for NMP determination: high performance liquid chromatography (HPLC), ion chromatography (IC), capillary electrophoresis (CE) and gas chromatography (GC). 5,6,[8][9][10] There are limitations associated with all these techniques. The HPLC method requires a mobile phase of pH 2 and the IC method uses a column temperature of 40 ˚C; both of these conditions could lead to degradation of cefepime and reduce measurement accuracy.…”

A degradation study of cefepime hydrochloride in solutions under various stress conditions by TLC–densitometry

“…The stress studies of cefepime was performed by HPLC and the degradation products were synthesized, isolated and characterized by various spectroscopic techniques (FT‐IR, NMR, MS) (Kumar et al ., ). The ion chromatographic method was developed for the determination of 1‐methylpyrrolidine in cefepime hydrochloride (Subramanian et al ., ). Diffuse reflectance mid‐infrared and powder X‐ray diffraction analyses were used to identify two different hydrated forms (dihydrate and monohydrate) of cefepime (Bugay et al ., ).…”