Stability-indicating RP-HPLC method for analysis of the antibiotic doripenem in pharmaceutical formulation—comparison to UV spectrophotometry and microbiological assay

Abstract

Summary.A stability-indicating liquid chromatographic (LC) method with UV detection was developed for the determination of doripenem in the marketed formulation (Doribax ® 500 mg, powder for injection). A forced degradation study was conducted according to available guidelines and main references. Thermal, oxidizing, acidic and basic stress conditions were assayed to show the stability-indicating power of the method. Chromatographic separation was achieved using an isocratic elution method in a reversed-phase system using a mobile phase prepared from phosphate buffer and acetonitrile. Extensive degradation was observed under thermal, oxidative and basic treatment, and the products formed were detected without interference in the analysis of doripenem. To verify the efficiency of chromatographic run, the system suitability was studied. The theoretical plates (N = 5498.3) and tailing factor (tf = 0.951) were constant during repeated injections. The retention time of doripenem was 7.35 min and the method was validated within the concentration range 5-50 μg mL −1 (r = 0.999). Adequate results were obtained that indicate repeatability (RSD % = 1.03-1.37), inter-day precision (RSD % = 0.51) and accuracy. In comparison to spectrophotometric and microbiological methods, statistical analysis showed no significant difference between the obtained results. The proposed method was successfully applied to doripenem quantification, showing it is applicable to determine the antibiotic in the presence of degradation products and also that is a reliable method for routine analysis.

Stability of doripenem in reconstituted solution – thermal and oxidative decomposition kinetics and degradation products by LC–MS

“…Analytical methods for quantitation of doripenem are well reported, involving drug monitoring in biological matrices (Dailly, Bouquié, Deslasndes, Jolliet, & Lefloch, ; Ikeda et al, ; Sutherland & Nicolau, ) and drug estimation on bulk and pharmaceuticals (Cielecka‐Piontek & Jelinska, ; Kathirvel & Devalarao, ; Mendez et al, ; Michalska, Pajchel, & Tyski, ). In the drug formulation, doripenem has been estimated by instrumental techniques such as HPLC, UPLC, UV and derivative spectrophotometry and capillary electrophoresis (Cielecka‐Piontek & Jelinska, ; Mantovani et al, ; Paliosa, Garcia, Schapoval, Mendez, & Steppe, ; Reddy et al, ), all assays being developed through experimental protocols applied to analytical validation and investigating the stability‐indicating profile. Concerning stability, some studies have investigated the chemical decomposition of doripenem in reconstituted samples (Crandon, Sutherland, & Nicolau, ; Psathas, Kuzmission, Ikeda, & Yasuo, ; Reddy et al, ).…”

Microbiological Analytical Method for Determination of Sertaconazole Nitrate in Pharmaceutical Formulations

“…gatifloxacin [11] and orbifloxacin [12] . From the literature review, it was concluded that different UVspectrophotometric and HPLC methods [13][14][15][16][17][18][19][20][21][22] are available for estimation of sertaconazole nitrate in pure and pharmaceutical dosage forms. There are no Microbiological analytical methods developed either by diffusion or turbidimetric method for the estimation of sertaconazole nitrate in pure and pharmaceutical dosage forms.…”