Smart Methods for Linezolid Determination in the Presence of Alkaline and Oxidative Degradation Products Utilizing Their Overlapped Spectral Bands

Abstract

UDC 535.243 and M. M. Abd El-Kawy a Linezolid (LIN) is considered the fi rst available oxazolidinone antibacterial agent. It is susceptible to hydrolysis and oxidation. Five simple, accurate, sensitive and validated UV spectrophotometric methods were developed for LIN determination in the presence of its alkaline (ALK) and oxidative (OXD) degradation products in bulk powder and pharmaceutical formulation. Method A is a second derivative one (D 2 ) in which LIN is determined at 240.9 nm. Method B is a pH-induced differential derivative one where LIN is determined using the fourth derivative (D 4 ) of the difference spectra (ΔA) at 285.3 nm. Methods C, D, and E are manipulating ratio spectra, where C is the double divisor-ratio difference spectrophotometric one (DD-RD) in which LIN was determined by calculating the amplitude difference at 243.7 and 267.6 nm of the ratio spectra. Method D is the double divisor-fi rst derivative of ratio spectra (DD-DD 1 ) in which LIN was determined at 270.2 nm. Method E is a mean centering of ratio spectra one (MCR) in which LIN was determined at 318.0 nm. The developed methods have been validated according to ICH guidelines. The results were statistically compared to that of a reported HPLC method and there was no signifi cant difference regarding both accuracy and precision.Introduction. Linezolid (LIN) or (S)-N-[[3-[3-fl uoro-4-(4-moropholinyl) phenyl]-2-oxo-5-oxazolidinyl] methyl] acetamide is considered the fi rst available oxazolidinone antibacterial agent. This is a new class of antimicrobials with good activity against Gram-positive bacteria. It possesses a unique mechanism of bacterial protein synthesis inhibition [1]. LIN shows strong activity against Gram-positive pathogens and is currently the only antibacterial agent that can be administered orally as well as intravenously with strong activity against methicillin-resistant Staphylococcus aureus. It may be particularly useful as an alternative to vancomycin in patients with renal function impairment, poor or no intravenous access, absence of glycopeptide tolerance, and those requiring outpatient therapy [2].A search of the literature reveals some LC methods for quantitation of LIN in tablets and in biological fl uids [3][4][5][6][7][8][9][10][11][12]. A chiral LC method has also been reported [13]. LIN was determined in the presence of its alkaline-induced degradation products using TLC densitometry, and D 1 and DD 1 methods [14]. Capillary zone electrophoresis was also applied for determination of LIN [15,16]. Its electrochemical characterization was also described [17]. The ICH guidelines [18] describe various stress conditions through which the stability of the active pharmaceutical ingredient (API) could be assessed. So, separation, identifi cation, quantifi cation, and characterization of the most probable and possible degradation products help in the improvement of the quality of API and its formulation.Most of the reported methods are based on chromatographic techniques requiring relatively high cost and long ana...