Metal Ion Leaching From Stainless Steel and Hastelloy in Common Pharmaceutical Solvents and the Impacts on Production and Analysis

Metal ions can cause issues in pharmaceutical production if they are too high or too low. Many studies have shown that ppb levels variation in iron, chromium, nickel, and manganese can all drastically impact pharmaceutical production, both upstream such as fermentation yields and downstream such as product oxidation, aggregation, denaturation, and other forms of degradation. Raw material suppliers work hard to keep metal levels in tight windows to not impact formulations, but then these materials are stored, distributed, and processed in stainless steel and/or hastelloy components. While steel and hastelloy are used due to their corrosion resistance, they are still alloys made of iron, chromium, nickel, and other elements and can leach these elements into solution at trace levels and cause problems. Little work has been published to quantify the metal ion leaching in various pharmaceutically relevant solvents from stainless steel and hastelloy alloys. Here, we present metal ion leaching data via ICP-MS along with a method to mitigate this metal ion leaching in the form of nano CVD silicon-based coating to block metal ion leaching into the solvent. Solvents will include water, methanol, and acetonitrile, both in their pure forms as well as in solution with citric acid, acetic acid, Tris HCl, Perchlorate salts, Guanadine HCl, Phosphoric acid, and potentially other relevant solutions. Results will show that by applying the coating to tubing, valves, filters, tanks, and any other metal processing equipment, metal ions can be limited to sub-ppb levels of leaching providing greater control over pharmaceutical processes.