Is It Essential to Use Anhydrous Acetonitrile in the Manufacture of Phosphorothioate Oligonucleotides?

It is demonstrated that acetonitrile containing up to at least 200 ppm water can be used as the wash solvent and to prepare the capping and sulfur transfer reagent solutions used in large-scale solid-phase phosphorothioate oligonucleotide synthesis, thus replacing most of the expensive anhydrous acetonitrile previously used. No compromise in yield or product quality is observed, compared to a control synthesis performed using anhydrous acetonitrile throughout.