Cefepime is a type of cephems used to treat various infections. According to the United States Pharmacopeia and the National Formulary (USP 42-NF 37*), quantification of N-methylpyrrolidine, an organic impurity, in the cefepime injection should be carried out with a 4.0 mm (I.D.) x 25 cm (length) column with L76 packing material in 5 μm particle size and meets following requirements. The use of two IC YK-421 columns (12.5 cm each) in series confirmed the requirements were met.
System suitability requirements:
Relative standard deviation (RSD) of N-methylpyrrolidine peak area: ≤ 4.0%
*The version at the time of the application acquisition.
In addition to the method validation, a commercial cefepime dihydrochloride for injection was analyzed using the method. The concentration of N-methylpyrrolidine found was 0.09 %, confirming the detected amount was below the allowable limit (1.0 %). In this method, cefepime elutes around 50 minutes. It is detectable by a UV detector, but rarely detected by a CD detector. It is noteworthy that using one YK-421 column alone fulfills the system suitability requirements and it is applicable for the quantification of N-methylpyrrolidine in commercial cefepime injections.
Sample : 10 μL each
(Sample solution) Commercial Cefepime hydrochloride formulation
Equivalent to 5 mg/mL of Cefepime hydrochloride in 0.002 N HNO3 aq.
(Standard solution) N-Methylpyrrolidine 0.05 mg/mL in 0.002 N HNO3 aq.
Columns : Shodex IC YK-421 (4.6 mm I.D. x 125 mm) x 2 Eluent : 0.01 N HNO3 aq./CH3CN=19/1 Flow rate : 1.0 mL/min Detector : Non-suppressed conductivity Column temp. : Room temp.