Validation of Capillary Electrophoresis Method for Determination of N-Methylpyrrolidine in Cefepime for Injection

Abstract

The present study relates to a new capillary electrophoresis method for the determination of N-methylpyrrolidine, an impurity considered to be toxic and also potential degradation impurity in cefepime hydrochloride drug substance. The newly developed capillary electrophoresis method for determining the content of N-methylpyrrolidine in cefepime for injection has been validated as per International Conference on Harmonization (ICH) guidelines to prove the selectivity, sensitivity, suitability, robustness, and ruggedness of the method. This simple, efficient, and rapid methodology may be used by pharmaceutical industry for routine analysis as well as during stability studies. The newly developed capillary electrophoresis method to determine the content of N-methylpyrrolidine in cefepime for injection requires 10 min for data acquisition, and uses an indirect UV photometry method to detect the analyte signal at 240 nm against the reference signal at 210 nm. The electrophoretic system is optimized to get stable base line, higher signal to noise ratio and peaks with narrow peak width. The method employs bare fused silica capillary with extended light path, effective length of capillary is 56 cm and inner diameter of capillary is 50 μm, 5 mmole of imidazole buffer adjusted to pH 5.1 with 3 molar acetic acid solution is used as background electrolyte. The sample is introduced in hydrodynamic mode employing pressure of 50 mbar for 5 s, and the desired separation is achieved with constant applied voltage of 25 kV at ambient temperature (~25°C).

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

“…It has been reported that an increase in the NMP level is proportional to the decline in the antibiotic potency of cefepime. 8,9 Monitoring the level of NMP in cefepime is, therefore, important for ensuring drug quality for clinical use and a threshold concentration of NMP in cefepime has been set at 0.3 % (w/w).…”

“…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.…”

Application of Silver Nanoparticles for the Spectrophotometric Determination of Cefdinir and Cefepime HCl in Pharmaceutical Preparations and Human Urine Samples

“…Cefepime or its content of N-methyl pyrrolidine were also determined by several methods such as HPLC [12,13], MEKC [14,15], GC [16,17], TLC [18,19], ion chromatography [20,21], spectrophotometry [22,23], spectrofluorimetry [24,25], voltammetry [26], capillary electrophoresis [27,28] and chemilluminescence [29].…”

Rapid analysis of N-methylpyrrolidine in cefepime with thermal desorption ion mobility spectrometry

“…Separation of NMP from cefepime has also been accomplished using capillary electrophoresis. [16] However, a significant issue with these techniques is the sample run times, all of these liquid phase techniques require a run time of several minutes to obtain a result. Since cefepime is unstable in solution the more rapidly a sample can be analysed the better, to avoid giving an artificially high level of NMP and 'false positive' results.…”