Development and Validation of an LC-MS/MS Assay for the Quantitation of MO-OH-Nap Tropolone in Mouse Plasma: Application to In Vitro and In Vivo Pharmacokinetic Studies

IF 4.2 2区化学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Molecules Pub Date : 2024-09-18 DOI:10.3390/molecules29184424

Wafaa N. Aldhafiri, Yashpal S. Chhonker, Nusrat Ahmed, Sandeep K. Singh, Staci L. Haney, James B. Ford, Sarah A. Holstein, Daryl J. Murry

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Abstract

A rapid, selective, and sensitive liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) method was developed and validated for the quantitation of MO-OH-Nap tropolone (MO-OH-Nap) in mouse plasma. MO-OH-Nap is an α-substituted tropolone with anti-proliferative properties in various cancer cell lines. Detection and separation of analytes was achieved on an ACE Excel C18 (1.7 µm, 100 × 2.1 mm, MAC-MOD Analytical, Chadds Ford, PA, USA) column with mobile phase consisting of 0.05% trifluoroacetic acid in water (mobile phase A) and 0.05% trifluoroacetic acid in acetonitrile (mobile phase B), with an isocratic elution of 15:85% (A:B) at a total flow rate of 0.25 mL/min. The LC-MS/MS system was operated at unit resolution in multiple reaction monitoring (MRM) mode, using precursor ion > product ion combination of 249.10 > 202.15 m/z for MO-OH-Nap and 305.10 > 215.05 m/z for the internal standard (IS), BA-SM-OM. The MS/MS response was linear over a concentration range of 1 to 500 ng/mL with a correlation coefficient (r2) of ≥0.987. The within- and between-batch precision (%RSD) and accuracy (%Bias) were within acceptable limits. The validated method was successfully applied to determine MO-OH-Nap metabolic stability, plasma protein binding, and bio-distribution studies of MO-OH-Nap in CD-1 mice.

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用于小鼠血浆中 MO-OH-Nap Tropolone 定量的 LC-MS/MS 分析方法的开发与验证：在体外和体内药代动力学研究中的应用

建立并验证了快速、选择性和灵敏的液相色谱-串联质谱（LC-MS/MS）方法，用于定量检测小鼠血浆中的MO-OH-Nap睾酮（MO-OH-Nap）。MO-OH-Nap是一种α-取代的睾酮，对多种癌细胞株具有抗增殖作用。分析物的检测和分离采用 ACE Excel C18（1.7 µm，100 × 2.1 mm，MAC-MOD Analytical，Chadds Ford，PA，USA）色谱柱，流动相为 0.05% 三氟乙酸水溶液（流动相 A）和 0.05% 三氟乙酸乙腈水溶液（流动相 B），等度洗脱比例为 15:85%（A:B），总流速为 0.25 mL/min。在多反应监测（MRM）模式下，LC-MS/MS 系统以单位分辨率运行，MO-OH-Nap 的前体离子 > 产物离子组合为 249.10 > 202.15 m/z，内标（IS）BA-SM-OM 为 305.10 > 215.05 m/z。在 1 至 500 毫微克/毫升的浓度范围内，MS/MS 反应呈线性关系，相关系数 (r2) ≥0.987。批内和批间精密度（%RSD）和准确度（%Bias）均在可接受范围内。该方法成功地应用于MO-OH-Nap在CD-1小鼠体内的代谢稳定性、血浆蛋白结合力和生物分布研究。

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来源期刊

Molecules 化学-有机化学

CiteScore

7.40

自引率

8.70%

发文量

7524

审稿时长

1.4 months

期刊介绍： Molecules (ISSN 1420-3049, CODEN: MOLEFW) is an open access journal of synthetic organic chemistry and natural product chemistry. All articles are peer-reviewed and published continously upon acceptance. Molecules is published by MDPI, Basel, Switzerland. Our aim is to encourage chemists to publish as much as possible their experimental detail, particularly synthetic procedures and characterization information. There is no restriction on the length of the experimental section. In addition, availability of compound samples is published and considered as important information. Authors are encouraged to register or deposit their chemical samples through the non-profit international organization Molecular Diversity Preservation International (MDPI). Molecules has been launched in 1996 to preserve and exploit molecular diversity of both, chemical information and chemical substances.