Glen Report 19.13: Technical Brief - Precautions During Packaging of Phosphoramidites and Transfer into Alternative Vials

As all of our customers are no doubt aware, phosphoramidites are moisture-sensitive. Indeed, by far the most common cause of poor performance of a phosphoramidite is the presence of moisture.

A critical component of Glen Research's quality management system (QMS) is the standard operating procedure (SOP) covering packaging of amidites into vials ready to be attached to synthesizers. When a new batch of a phosphoramidite is produced and approved by QC, the most urgent task is to package it efficiently. The only way to preserve its integrity and maintain a high coupling efficiency even after months of storage, is to package this bulk into end-user vials within a few days. At this point, we use historical sales data along with information on pending orders to determine which pack sizes and vial types to elect to weigh. In particular for our more exotic products, we dispense the majority into standard slider (ABI type) vials. These vials are shipped with a clean, dry empty vial/bottle corresponding to the synthesizer type.

We are, of course, able to do special packaging if it is in phase with our production and QC schedules.

It is important to remember that some phosphoramidites are white or colored powders after purification and isolation while other products do not crystallize and stay as viscous oils. These oil-products have specific features and risks. Among them are the Spacers, Chemical Phosphorylation Reagents and the vast majority of non-nucleosidic modifiers.

Due to their nature, these oil-products form a thin film once transferred and dried in end-user vials and are impossible to transfer, without first dissolving them again. Also, oils are just as hygroscopic as powders.?If we were to redissolve these oils for transfer to user-specified vials, we could no longer guarantee that the product would accurately conform to the data on the Certificate of Analysis. Consequently, we have never transferred such products and they are always shipped together with an appropriate empty bottle, corresponding to the customer’s synthesizer type.?

Also it is important to remember that, sometimes, oils are difficult to dissolve. And again, they can pick up moisture as fast as powders.?So we recommend doing any synthesis with these products using fresh diluent (anhydrous acetonitrile, less than 25 ppm of water). Using a fresh disposable (or dried glass) syringe, draw the acetonitrile through the septum of the diluent bottle and inject this acetonitrile into the “oil-amidite” vial through the septum, to avoid moisture exposure. Then swirl occasionally over several minutes until the oil is completely dissolved and forms a homogenous solution, which occurs when no wavy lines of concentration gradient are observed. Some of the more viscous oils may require between 5 and 10 minutes.?Use care to maintain anhydrous conditions. Then transfer the solution to the alternate vial type (when necessary), again using a syringe, and make sure the final pre-dried recipient vial (from Glen Research or pre-dried by the user) is opened at the very last minute.

For use of an expensive amidite on an Expedite synthesizer, you may prefer to use a vial with an internal conical shape that makes small sample handling easy and convenient and allows maximum delivery of your amidite solutions. V-vials from Wheaton or Reacti-vials from Pierce are available in 2, 3 or 5 mL size and with the 20-400 neck that is directly compatible with the Expedite amidite port.

Finally a description of our products (powder or oil) is mentioned on the Certificate of Analysis that we provide with each product. Specific information about dissolution and special instructions are written on this Certificate, when applicable. So please do not forget to check this important information before using the product.