Development and Validation of an HPLC Assay For Dual Detection of Gentamicin Sulfate and Leucine From a Novel Dry Powder For Inhalation

Abstract

TM ; Dual de- tection; Dry powder; Inhalation Abstract A stability indicating HPLC assay with UV detection was developed for the simultaneous quantification of Gentamicin Sulfate and L-leucine from NanoGENT™ dry powder for inhalation. In order to support the development of the NanoGENT™ (dry powder Gentamicin Sulfate for inhalation) the assay was created to allow simultaneous detection of the active pharmaceutical ingredient (Gentamicin Sulfate) and the primary excipient (L-leucine). In order to quantify Gentamicin Sulfate by UV detection derivatization was required. The assay resolved L-leucine from all four Gentamicin Sulfate peaks and all four Gentamicin Sulfate peaks from each other with a reversed phase isocratic assay. Once developed the assay was validated in accordance with regulatory guidance in order to support regulatory approval of the NanoGENT™ dry powder inhalation formulation. The validation data indicated that the dual detection assay meets or exceeded all criteria for use as a stability indicating assay. Orally inhaled therapeutics are a mainstay in the treatment of asthma and COPD and is growing rapidly in the treatment of other pulmonary and systemic indications. The growth of orally inhaled therapeutics to treat atypical indications has broadened beyond vaccines and insulin to include biological threats. This growth has exacerbated the fact that there are currently a minimal number of GRAS excipients for inhalation delivery (1). Further, the excipients that are considered GRAS do not span the range of physical chemical properties that are often required for formulations of a material for delivery to the lungs.