Development and Validation of Stability Indicating HPLC Method for the Determination of Related Substances in Droxidopa Drug Substance.

Abstract

Droxidopa, a synthetic amino acid precursor to norepinephrine, was licensed by the FDA in 2014 to treat neurogenic OH. The enzyme L-amino acid decarboxylase in sympathetic neurons converts Droxidopa to norepinephrine, which raises the amount of norepinephrine in the blood.1 Because noradrenaline crosses the blood-brain barrier poorly. Droxidopa is used to raise the concentration of noradrenaline in the brain instead of noradrenaline itself. It is recommended for the treatment of dopamine beta-hydroxylase deficiency, non-diabetic autonomic neuropathy, orthostatic dizziness, and lightheadedness in adult patients with symptomatic neurogenic orthostatic hypotension resulting from primary autonomic failure (Parkinson’s disease, multiple system atrophy, and pure autonomic failure.2-5 It is a synthetic analog of catecholamine acid that raises norepinephrine and epinephrine levels throughout the body by being immediately metabolized by dopa-decarboxylase. In the CNS, it also penetrates the blood-brain barrier to carry out its pharmacological actions. Through the induction of peripheral arterial and venous vasoconstriction, it raises blood pressure peripherally and causes slight, momentary increases in plasma norepinephrin.