title: Approach to evaluating dried blood spot sample stability during drying process and discovery of a treated card to maintain analyte stability by rapid on-card pH modification.
abstract: Unstable drug candidates often lead to complexity for both sample collection and bioanalysis. Dried blood spot (DBS) technology is believed to be a viable solution to address this problem. However, it is currently a challenge to evaluate compound stability on DBS due to its solid format. The observed compound loss on a DBS card could be degradation and/or incomplete recovery. Therefore, a reliable bioanalytical method which can differentiate recovery loss from degradation is necessary for such stability evaluation. In this paper, the stability of an unstable drug candidate (KAI-9803) in human blood was evaluated using DBS. A reliable approach to evaluating analyte stability on DBS was developed with an appropriate time-zero sample, a consistent DBS sample processing method, and a suitable positive control. Commercially available DBS cards were evaluated, and it was found that KAI-9803 degraded during the drying process. An in-house modified DBS card was developed and demonstrated to be able to stabilize KAI-9803 during the drying process by rapidly lowering the pH of the spotted blood sample. The storage stability of KAI-9803 in human blood on this new card has been established for at least 48 days at room temperature. This in-house modified DBS card could provide a generic approach for other compounds which require stabilization at a low pH.
authors: Bioanalytical Sciences, Research & Development, Bristol-Myers Squibb Company, Route 206 and Province Line Road, Princeton, New Jersey 08543, USA. guowen.liu@bms.com
authors: Guowen
authors: G
authors: Liu
authors: Qin C
authors: QC
authors: Ji
authors: Mohammed
authors: M
authors: Jemal
authors: Adrienne A
authors: AA
authors: Tymiak
authors: Mark E
authors: ME
authors: Arnold
mesh_terms: D002851:Chromatography, High Pressure Liquid; D019343:Citric Acid / Q000737:chemistry; D059788:Dried Blood Spot Testing; D004355:Drug Stability; D006801:Humans; D006863:Hydrogen-Ion Concentration; D010455:Peptides / Q000097:blood*; D053719:Tandem Mass Spectrometry; D013696:Temperature
chemical_list: C527142:KAI 9803; D010455:Peptides; D019343:Citric Acid