{Reference Type}: Journal Article
{Title}: A drug-excipient interaction impurity of bromhexine hydrochloride injection: Structure and formation mechanism elucidation.
{Author}: Zhou M;Wu W;Pu H;Chen F;Yi C;Long Y;
{Journal}: J Pharm Biomed Anal
{Volume}: 247
{Issue}: 0
{Year}: 2024 Sep 1
{Factor}: 3.571
{DOI}: 10.1016/j.jpba.2024.116256
{Abstract}: A long-term stability study using high performance liquid chromatography (HPLC) revealed an unidentified impurity in the bromhexine hydrochloride injection, which was employed as a mucolytic agent. Investigations into stress degradation and elemental impurities revealed one of the elemental impurities Fe3+ in this injection as the primary generator of these impurities. This impurity, named N-carboxymethyl bromhexine, was a product formed during drug-excipient interaction between bromhexine and tartaric acid with Fe3+. The structure of the impurity was identified through ultra-high-performance liquid chromatography with diode array detector (UHPLC-DAD), liquid chromatograph mass spectrometer (LC-MS). Further, the formation mechanism of the impurity was discussed. Overall, this study elucidates the cause, origin, and mechanism of an unknown impurity in bromhexine hydrochloride injection, providing a basis for quality control for bromhexine hydrochloride injections and drug products containing both amine and tartaric acid.