A Generic UHPLC/UV/MS Method for Cleaning Verifi cation of Highly Potent Drugs

Cleaning validation (CV) is a Good Manufacturing Practices (GMP) requirement in manufacturing of drug substances and drug products. Liquid Chromatography with UV detection is a common choice for cleaning verifi cation studies for most drugs at sensitivity levels of approximately 20–50 ng/mL. For highly potent drugs, CV methods to reach sensitivity levels of low ng/mL can be implemented using UV detection with an extended pathlength fl ow cell or mass spectrometric detection. The sensitivity of UHPLC/MS method using an Agilent Jet Stream source on an Agilent 6150 Series Single Quadrupole LC/MS shows even lower limits of quantitation (LOQ) of approximately 0.5 ng/mL. In addition, higher injection volumes can further lower LOQs. This study shows a 2-minute generic cleaning verifi cation method in a concentration range of 0.5 ng/mL to 1,000 ng/mL for fi ve model drug compounds. This generic cleaning verifi cation assay method can often be adapted to many different drugs with minimum efforts in method development, qualifi cation, and transfer. This Application Note also shows the identifi cation of unknown compounds employing a user-supplemented NIST Mass Spectral Search Program. A Generic UHPLC/UV/MS Method for Cleaning Verifi cation of Highly Potent Drugs