Quantification of pharmaceutical peptides in human plasma by LC-ICP-MS sulfur detection

Abstract

A method for quantification of a pharmaceutical peptide in human plasma was developed using gradient elution LC-ICP-MS. A membrane desolvation (MD) system was applied to remove organic solvents from the eluent prior to the detection as SO⁺ in the dynamic reaction cell (DRC) of the ICP-DRC-MS instrument and subsequent quantification by post-column isotope dilution (IDA). Plasma proteins were precipitated prior to analysis. Analytical figures of merit including linearity, precision, LOD, LOQ and accuracy were considered satisfactory for analysis of plasma samples. The selectivity of the developed method was demonstrated for five pharmaceutically relevant peptides: desmopressin, penetratin, substance P, PTH (1-34) and insulin. Preliminary experiments on an ICP-MS/MS system using oxygen to reduce the effect of organic solvents were also performed to compare sensitivity. The results of the study demonstrated that LC-ICP-MS post-column IDA may constitute a valuable additional tool in quantification of non-labelled peptides in the early drug development offering absolute quantification without need of species specific standards.