Paired-Fraction Electrochemical Programming for Oxytocin Manufacture: A Falsifiable Strategy for Single-Disulfide Ring Closure and Process Stability

Oxytocin is a nine-residue amidated peptide whose pharmacological conformation depends on a single Cys1-Cys6 disulfide. This article applies paired-fraction electrochemical programming (PFEP) to the post-assembly manufacture of oxytocin. In PFEP, anodic and cathodic liquids are produced in a divided cell, quantified as transferable acid-base and redox capacities, and dosed into an electrode-free peptide reactor. The proposed role is not peptide-bond formation from free amino acids and not a persistent “activated water” state. It is feedback control of cysteine deprotection or reduction, intramolecular oxidation, and termination before disulfide interchange, oligomerization, or irreversible side-chain oxidation. The central hypothesis is that a low-concentration, time-separated state-dose trajectory can widen the interval in which monomeric cyclic oxytocin predominates. A complete protocol is proposed from reduced linear precursor through fraction qualification, programmed oxidation, LC-MS endpoint detection, purification, and formulation hand-off. Chemically reconstructed pH/redox trajectories, static buffer, premixed fractions, and conventional air or reagent oxidation are mandatory controls. The concept is rejected if those controls reproduce the outcome without a measurable manufacturing advantage. No experimental yield, potency, or shelf-life claim is made. Article type: Perspective, mechanistic hypothesis, and experimental framework. No experimental peptide yield, potency, clinical effect, or shelf-life evidence is reported.