Stable isotope labeling (SIL) of active pharmaceutical ingredients (API) is a well-established technique for the accurate quantification of small-molecule drugs. As the scope of active ingredients is expanding into areas of larger molecules, such as oligonucleotides (ONs), the development of new quantification techniques is critical. Herein, we describe the analysis of a ³⁴S-SIL anti-PCSK9 gapmer-type antisense ON. A new method for the quantification of this API in complex biological matrices was developed and applied to mouse, dog, and monkey tissue homogenates, which gave improved accuracy and reproducibility compared with the use of auxiliary ONs as internal standard.

中文翻译：

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PCSK9-活性寡核苷酸的 34S-SIL 作为质谱准确定量的工具

活性药物成分 (API) 的稳定同位素标记 (SIL) 是一种成熟的小分子药物准确定量技术。随着活性成分的范围扩展到更大的分子领域，例如寡核苷酸 (ON)，开发新的量化技术至关重要。在此，我们描述了对³⁴ S-SIL 抗 PCSK9 gapmer 型反义 ON 的分析。开发了一种在复杂生物基质中定量该 API 的新方法，并将其应用于小鼠、狗和猴子组织匀浆，与使用辅助 ONs 作为内标相比，该方法提高了准确性和重现性。