Pharmaceutical cleaning validation using non-proximate large-area desorption electrospray ionization mass spectrometry

Abstract

Desorption electrospray ionization (DESI) is a droplet-based ionization method that is applied to samples in the ambient environment with little or no sample preparation. Its utility for industrial applications is explored here for the case of pharmaceutical cleaning validation. A non-proximate large-area DESI system was built to examine representative areas of the surfaces of reaction vessels used in active product ingredient (API) manufacturing. A large-area sprayer capable of sampling an area of ∼2.5 cm² was coupled with a transport tube to allow sensitive, representative sampling of APIs from a stainless steel surface 1 m away from the mass spectrometer. The system was used to detect the APIs neostigmine, acebutolol, amiloride, amiodarone, ibuprofen, montelukast, potassium clavulanate, and β-estradiol, at levels as low as 30–10 ng/cm², easily satisfying the general acceptable limits set by the pharmaceutical industry. These levels were achieved from surfaces resembling the equipment used in API manufacturing processes at a rate of 30 s per analysis. Copyright © 2008 John Wiley & Sons, Ltd.