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

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• 作者：Guowen Liu ; Qin C. Ji ; Mohammed Jemal ; Adrienne A. Tymiak ; Mark E. Arnold
• 刊名：Analytical Chemistry
• 出版年：2011
• 出版时间：December 1, 2011
• 年：2011
• 卷：83
• 期：23
• 页码：9033-9038
• 全文大小：784K
• 年卷期：v.83,no.23(December 1, 2011)
• ISSN：1520-6882

文摘

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.