制剂和组织中 IR780 的定量测量。

Quantitative measurements of IR780 in formulations and tissues.

机构信息

Department of Pharmaceutical Sciences, University of North Texas Health Science Center, Fort Worth, TX, USA.

Department of Chemistry, University of North Texas, Denton, TX, USA.

出版信息

J Pharm Biomed Anal. 2021 Feb 5;194:113780. doi: 10.1016/j.jpba.2020.113780. Epub 2020 Nov 20.

DOI:10.1016/j.jpba.2020.113780

PMID:33280993

Abstract

PURPOSE

IR780 iodide, a promising near-infrared dye, is widely used to prepare nanoparticles as a theranostic agent for tumor imaging and therapy. However, there are no validated (bio)analytical methods to measure IR780 in nanoparticles and tissues in literature. The aim of this study is to develop and validate a new HPLC method to measure IR780 concentration in IR780 formulations as well as a new LC-MS/MS method to measure IR780 concentration in tissue samples, particularly in liver and lung.

MATERIALS AND METHODS

IR780 granules that produced IR780 in situ self-assembled nanoparticles upon contact with water were prepared at two drug loadings (0.2 % and 0.37 %). An HPLC method was developed and validated to measure IR780 concentrations in IR780 granules and nanoparticles. Furthermore, a validated LC-MS/MS method was developed to measure IR780 in mouse liver and lung. Both HPLC method and LC-MS/MS method were validated in terms of specificity, stability, linearity, limit of detection, limit of quantification, accuracy and precision.

RESULTS

Both HPLC method and LC-MS/MS method achieved the criteria for method validation. The HPLC method was accurate in the concentration range of 0.5-25 μg/mL. The measured drug loadings were 95 % of the theoretical drug loadings. The validated LC-MS/MS method can quantitatively measure the concentrations of IR780 in liver and lung. The linear range of the LC-MS/MS method was 1-1000 ng/mL for both liver and lung samples. IR780 granules showed the lung selectivity compared to IR780 solution at 2 h after oral administration.

CONCLUSION

A validated HPLC method was developed to measure IR780 concentration in pharmaceutical formulations and a validated LC-MS/MS method was developed to measure IR780 concentration in tissues. These quantitative methods provide reliable measurements of IR780 in pharmaceutic formulations and biological samples, which will significantly facilitate the research of IR780 as a theranostic agent for cancer therapy and imaging.

摘要

目的

IR780 碘化物是一种很有前途的近红外染料，广泛用于制备纳米颗粒作为肿瘤成像和治疗的治疗药物。然而，目前还没有经过验证的（生物）分析方法来测量文献中纳米颗粒和组织中的 IR780。本研究的目的是开发和验证一种新的 HPLC 方法来测量 IR780 制剂中的 IR780 浓度，以及一种新的 LC-MS/MS 方法来测量组织样品中的 IR780 浓度，特别是在肝脏和肺部。

材料与方法

IR780 颗粒在与水接触时就地自组装成纳米颗粒，制备了两种药物载药量（0.2%和 0.37%）。开发并验证了一种 HPLC 方法来测量 IR780 颗粒和纳米颗粒中的 IR780 浓度。此外，还开发了一种经验证的 LC-MS/MS 方法来测量小鼠肝和肺中的 IR780。HPLC 方法和 LC-MS/MS 方法均在专属性、稳定性、线性、检测限、定量限、准确度和精密度方面进行了验证。

结果

HPLC 方法和 LC-MS/MS 方法均达到了方法验证的标准。HPLC 方法在 0.5-25 μg/mL 的浓度范围内准确。测量的药物载药量为理论药物载药量的 95%。验证后的 LC-MS/MS 方法可定量测量肝和肺组织中 IR780 的浓度。LC-MS/MS 方法的线性范围为肝和肺样本的 1-1000ng/mL。与口服后 2 小时的 IR780 溶液相比，IR780 颗粒显示出对肺的选择性。