dropletProbe mass spectrometry (MS) is an emerging tool for the rapid ex vivo analysis of drugs in tissues and whole-body sections. Its use has been demonstrated to better understand a drug's absorption, distribution, metabolism, and excretion (ADME) properties. To further optimize the overall utility of this technique, it is important to characterize and understand the various tissue matrix effects and extraction solvents on the overall performance of dropletProbe MS analyses. Herein, we systematically evaluated the impact of extraction solvents and various tissues on the relative detected signal intensities of a test set of diverse drugs. It was observed that the tissue matrix had a minimal effect on the performance of dropletProbe MS for the limited set of tested compounds once an optimized extraction solvent was identified. A general starting extraction solvent of 1:1 acetonitrile/water (v:v) was identified to efficiently extract the test set of compounds from various tissues. Next, the optimized conditions were used to map the distribution of the drug diclofenac and its metabolites in whole-body mouse sections. The relative tissue distribution of diclofenac and its metabolites, including the phase II acyl-glucuronide metabolite, were successfully determined with the technique. It is recommended these conditions are used as a general guideline when initiating dropletProbe MS studies of therapeutic drug-like compounds.

中文翻译：

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用于药物样分子全身组织分布分析的液滴探针质谱优化。

dropletProbe 质谱 (MS) 是一种新兴工具，用于对组织和全身切片中的药物进行快速离体分析。它的使用已被证明可以更好地了解药物的吸收、分布、代谢和排泄 (ADME) 特性。为了进一步优化该技术的整体效用，重要的是要表征和了解各种组织基质和提取溶剂对 dropletProbe MS 分析整体性能的影响。在此，我们系统地评估了提取溶剂和各种组织对不同药物测试集的相对检测信号强度的影响。据观察，一旦确定了优化的提取溶剂，组织基质对有限的一组测试化合物的 dropletProbe MS 性能的影响最小。确定了 1:1 乙腈/水 (v:v) 的通用起始提取溶剂，以有效地从各种组织中提取测试组化合物。接下来，使用优化的条件来绘制药物双氯芬酸及其代谢物在小鼠全身切片中的分布图。使用该技术成功测定了双氯芬酸及其代谢物（包括 II 期酰基葡萄糖醛酸苷代谢物）的相对组织分布。建议将这些条件用作启动治疗药物类化合物的 dropletProbe MS 研究时的一般准则。优化条件用于绘制药物双氯芬酸及其代谢物在小鼠全身切片中的分布图。使用该技术成功测定了双氯芬酸及其代谢物（包括 II 期酰基-葡糖苷酸代谢物）的相对组织分布。建议将这些条件用作启动治疗药物类化合物的 dropletProbe MS 研究时的一般准则。优化条件用于绘制药物双氯芬酸及其代谢物在小鼠全身切片中的分布图。使用该技术成功测定了双氯芬酸及其代谢物（包括 II 期酰基-葡糖苷酸代谢物）的相对组织分布。建议将这些条件用作启动治疗药物类化合物的 dropletProbe MS 研究时的一般准则。