Cleaning verification assays for highly potent compounds by high performance liquid chromatography mass spectrometry: strategy, validation, and long-term performance.
A cleaning-verification assay was validated for a highly potent family of compounds utilizing a swab-sampling procedure and high performance liquid chromatography mass spectrometry (LC-MS) for separation and detection of the analytes. Due to the high potency of the compound, the LC-MS method was validated at a level of 50 ng/25 cm(2) and 50 ng/100 cm(2) (which equates to 10 ng/ml after extraction in 5 ml of sample solvent, and 3 ng/ml after correction for sampling losses). This validation exercise included recovery estimates from all drug product contact surfaces within the clinical trial manufacturing equipment, namely, stainless steel, anodized aluminum, Rilsan coated aluminum, bronze, polyvinylchloride, and Oilon. The limit of detection for the LC-MS method was determined to be less than 0.5 ng/ml, or less than 0.1 ng/cm(2), of the analyte. This method does not employ an internal standard. Long-term performance of the validated method is also reported. The precision on replicate injections of the standard prepared in the range of 3-6 ng/ml was typically better than 8.0% relative standard deviation (R.S.D.) over the course of 1 year, which resulted from 10 cleaning-verification submissions. Those results were consistent with the data obtained during method validation.
Liu
Li
L
Eli Lilly and Company, Analytical Sciences Research and Development, Lilly Research Laboratories, Indianapolis, IN, USA. l.liu@lilly.com
Pack
Brian W
BW
D000085:Acetates / Q000032:analysis*; D019342:Acetic Acid / Q000032:analysis*; D000180:Acrylic Resins / Q000737:chemistry; D000497:Alloys / Q000737:chemistry; D000535:Aluminum / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D003666:Decontamination / Q000379:methods*; D013058:Mass Spectrometry / Q000379:methods*; D000432:Methanol / Q000032:analysis*; D011143:Polyvinyl Chloride / Q000737:chemistry; D015203:Reproducibility of Results; D013193:Stainless Steel / Q000737:chemistry; D013499:Surface Properties
D000085:Acetates; D000180:Acrylic Resins; D000497:Alloys; D013193:Stainless Steel; C010504:polyacrylonitrile; D011143:Polyvinyl Chloride; D000535:Aluminum; D019342:Acetic Acid; C018824:ammonium acetate; D000432:Methanol