Development and validation of a method to study the mixture daptomycin/heparine in ringer lactate by high performance liquid chromatography (HPLC)

Abstract

Background In patients with infection related to catheter (IRC) is needed to consider several aspects that will lead both the managing and treatment of them. When the retention of the catheter is advisable it is necessary to apply technologies of sealed antibiotic. With that aim, the mixture daptomicine/heparine prepared in ringer lactate solution has been proposed to be used. Purpose The purpose of this research has been to study the mixture daptomicine/heparine sodium prepared in ringer lactate solution since no information upon its chemical and physical compatibility has been found in the consulted bibliography. A high performance liquid chromatography method (HPLC) has been developed following the International Conference on Harmonisation guidelines (ICHs) for this purpose. Materials and methods The chromatographic separation was performed in a C-18 column. Due to the complexity of the mixture, it was necessary to apply a gradient in the mobile phase to achieve complete separation of the compounds, also to get separation from the degradation products of daptomicine. The started mobile phase composition was water /acetonitrile containing 0.1% of trifluoroacetic (60%:40%). The entire compounds were separated in 10 min. The detection was performed using a Diode Array Detector. Results The linearity, accuracy, reproducibility, robustness and specificity of this HPLC method have been validated following the ICH guidelines. In fact, the HPLC method considered the degradation products that were detected when the mixture was submitted to accelerated stress conditions. The method was optimised to ensure that degradation products will not interference in the determination of daptomicine/heparine when analysing the mixture. Recoveries higher than 90.0% of the initial concentration were found when analysing the mixture daptomicine/heparine in ringer sodium lactate in preloaded syringes in a long term stability study (15 days). Conclusions The method here propose has been validated following the ICH guidelines to be used as indicating-stability one. Thus, it has been used in the stability study of the mixture daptomicine/heparine in ringer sodium lactate in preloaded syringes since no information has been previously published about its chemical and physical compatibility. This study has demonstrated the stability of the mixture during the time tested (15 days).