In recent years, an increase in the discovery and development of biotherapeutics employing new modalities, such as bioconjugates or novel routes of delivery, has created bioanalytical challenges. The inherent complexity of conjugated molecular structures means that quantification of the bioconjugate and its multiple components is critical for preclinical/clinical studies to inform drug discovery and development. Moreover, bioconjugates involve additional multifactorial complexity because of the potential for in vivo catabolism and biotransformation, which may require thorough investigations in multiple biological matrices. Furthermore, excipients that enhance absorption are frequently evaluated and employed for the development of oral and inhaled biotherapeutics. Risk-benefit assessments are required for novel or existing excipients that utilize dosages above previously approved levels. Bioanalytical methods that can measure both excipients and potential drug metabolites in biological matrices are highly relevant to these emerging bioanalysis challenges. We discuss the bioanalytical strategies for analyzing bioconjugates such as antibody-drug conjugates and antibody-oligonucleotide conjugates and review recent advances in bioanalytical methods for the quantification and characterization of novel bioconjugates. We also discuss bioanalytical considerations for both biotherapeutics and excipients through novel administration routes and review analyses in various biological matrices, from the extensively studied serum or plasma to tissue biopsy in the context of preclinical and clinical studies from both technical and regulatory perspectives.

中文翻译：

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解决新型生物偶联物和生物治疗药物输送路线日益复杂的生物分析方法和战略观点。

近年来，采用新模式（例如生物偶联物或新型递送途径）的生物治疗药物的发现和开发不断增加，这给生物分析带来了挑战。共轭分子结构的固有复杂性意味着生物共轭物及其多种成分的量化对于临床前/临床研究以告知药物发现和开发至关重要。此外，由于体内分解代谢和生物转化的潜力，生物偶联物涉及额外的多因素复杂性，这可能需要对多种生物基质进行彻底研究。此外，增强吸收的赋形剂经常被评估并用于口服和吸入生物治疗药物的开发。对于使用剂量高于先前批准水平的新型或现有辅料，需要进行风险效益评估。可以测量生物基质中赋形剂和潜在药物代谢物的生物分析方法与这些新兴的生物分析挑战高度相关。我们讨论了用于分析生物偶联物（例如抗体-药物偶联物和抗体-寡核苷酸偶联物）的生物分析策略，并回顾了用于定量和表征新型生物偶联物的生物分析方法的最新进展。我们还通过新颖的给药途径和对各种生物基质的回顾分析，讨论了生物治疗药物和赋形剂的生物分析注意事项，