Method for the determination of residual formaldehyde in an inactivated Zika vaccine formulated with aluminum hydroxide gel.

A simple method for the determination of low levels of residual formaldehyde in an inactivated Zika vaccine formulated with aluminum hydroxide gel was developed for the assessment of drug product quality. Formaldehyde was reacted with 2,4-dinitrophenylhydrazine (DNPH) and the derivatized product was detected by HPLC with an UV detector at 360 nm. The derivatization reaction could be carried out in a 2-mL HPLC vial and the sample was analyzed directly. The method was fully validated according to the International Conference on Harmonization Q2 guidelines. Aluminum hydroxide gel up to 1.0 mg/mL (aluminum concentration) did not interfere with the determination of formaldehyde in drug product. Formaldehyde concentrations of 0.05 μg/mL (quantitation limit) to 1.00 μg/mL in the Zika vaccine could be precisely determined. Hence, this method proved to be suitable for quality control of the Zika vaccine.