%0 Journal Article
%T A Validated New Gradient Stability-Indicating LC Method for the Analysis of Doripenem in Bulk and Injection Formulation
%A Singaram Kathirvel
%A Garikapati Devalarao
%J Chromatography Research International
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/963595
%X A sensitive, precise, specific, linear, and stability-indicating gradient HPLC method was developed for the estimation of doripenem in active pharmaceutical ingredient (API) and in injectable preparations. Chromatographic separation was achieved on C18 stationary phase with a mobile phase gradient consisting of acetonitrile, methanol, and pH 5.2 phosphate buffer. The mobile phase flow rate was 0.8£¿mL/min, and the eluted compounds were monitored at 210£¿nm. The method is linear over the range of 0.335 to 76.129£¿¦Ìg/mL. The correlation coefficient was found to be 0.999. The numbers of theoretical plates and tailing factor for doripenem were 53021 and 0.9, respectively. Doripenem was subjected to the International Conference on Harmonization (ICH) prescribed hydrolytic (acid, base, and neutral), oxidative, photolytic, and thermal stress conditions. Among all the above-mentioned conditions, the drug was found to be stable under photolytic degradation. Peak homogeneity data for doripenem in the chromatograms from the stressed samples obtained by use of the photodiode array detector demonstrated the specificity of the method for analysis of doripenem in presence of the degradation products. The performance of the method was validated according to the present ICH guidelines for specificity, limit of detection, limit of quantification, linearity, accuracy, precision, and robustness. 1. Introduction Doripenem (S-4661) (Figure 1) is a recently developed member of the carbapenem class of beta-lactam antibiotics. Similarly to meropenem and ertapenem, but unlike imipenem, doripenem has a 1-¦Â-methyl side chain that provides resistance to the renal enzyme I-dehydropeptidase. Doripenem has been shown to have broad-spectrum activity against Gram-negative and Gram-positive pathogens including strains of Pseudomonas aeruginosa [1, 2]. Doripenem, like other carbapenems, was developed for the treatment of hospitalized patients with moderate or severe bacterial infections [3]. Figure 1: Structure of doripenem. An extensive literature survey revealed that there are certain methods reported on the stability of doripenem both in solid state and solutions [4¨C13]. In our knowledge and after an exhaustive revision of the literature, there is no evidence about the stability indicating gradient HPLC assay method of this drug in bulk and its formulation. Moreover, an official method for its determination has not been yet described in any Pharmacopoeia. Consequently, the implementation of an analytical methodology to determine doripenem in API and its formulation is a pending challenge
%U http://www.hindawi.com/journals/cri/2013/963595/