Incompatibility between Meropenem Injection and Amino Acid Infusions caused by L-Cysteine

Abstract

After meropenem hydrate (MEPM) injection and amino acid infusions are mixed, the MEPM residual ratio sequentially decreases. This incompatibility is probably due to the nucleophilic attack on the β-lactam ring of MEPM by L-cysteine (L-Cys) present in the amino acid infusion. This study aims to identify the influence of L-Cys on the reaction between MEPM injection and amino acid infusions through an initial incompatibility test between MEPM and L-Cys at pH 4 to 8, followed by an incompatibility test between MEPM injection (MEPM plus additives) and 18 types of amino acid infusions. In the MEPM and L-Cys incompatibility test, as the pH increased, the MEPM decomposition speed was observed to increase after mixing of the two components. This reaction progressed as a secondary reaction, the linear relationship between pH and the logarithm of secondary reaction speed constant, k₂, was established (ln k₂ = 1.632 × pH － 15.631, r² = 0.998). In the incompatibility test between MEPM injection and amino acid infusions, as the concentration of L-Cys increased, the MEPM residual ratio was observed to decrease. At 10 and 30 minutes after the mixture of components, a strong correlation was observed between the estimated MEPM residual ratio from the reaction velocity and the measured value (10 minutes: r² = 0.985, RMSE: 5.44％; 30 minutes: r² = 0.986，RMSE: 4.55％). The results above indicate that the residual ratio of MEPM obtained through the L-Cys incompatibility test matches the measured residual ratio of MEPM using the MEPM injection and amino acid infusions. Therefore, L-Cys has been identified as the main cause of incompatibility between MEPM injection and amino acid infusions.