Gervazoni Luiza F O, Gonçalves-Ozorio Gabriella, Ferreira-Paes Taiana, Silva Aline C A, Silveira Gabriel P E, Pereira Heliana M, Pinto Douglas P, Cunha-Junior Edézio F, Almeida-Amaral Elmo E
Laboratório de Bioquímica de Tripanosomatídeos, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.
Laboratório de Farmacocinética, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.
Front Chem. 2023 Mar 9;11:1016193. doi: 10.3389/fchem.2023.1016193. eCollection 2023.
Given the lack of investments, structure, and difficulty of metabolite isolation, promising natural product studies do not progress to preclinical studies, such as pharmacokinetics. 2'-Hydroxyflavanone (2HF) is a flavonoid that has shown promising results in different types of cancer and leishmaniasis. For accurate quantification of 2HF in BALB/c mouse blood, a validated HPLC-MS/MS method was developed. Chromatographic analysis was performed using C (5μm, 150 mm × 4.6 mm). The mobile phase consisted of water containing 0.1% formic acid, acetonitrile, and methanol (35/52/13 v/v/v) at a flow rate and total running time of 0.8 mL/min and 5.50 min, respectively, with an injection volume of 20 µL. 2HF was detected by electrospray ionization in negative mode (ESI-) using multiple reaction monitoring (MRM). The validated bioanalytical method showed satisfactory selectivity without significant interference for the 2HF and IS. In addition, the concentration range between 1 and 250 ng/mL showed good linearity (r = 0.9969). The method showed satisfactory results for the matrix effect. Precision and accuracy intervals varied between 1.89% and 6.76% and 95.27% and 100.77%, respectively, fitting the criteria. No degradation of 2HF in the biological matrix was observed since stability under freezing and thawing conditions, short duration, postprocessing, and long duration showed deviations less than 15%. Once validated, the method was successfully applied in a 2HF oral pharmacokinetic study with mouse blood, and the pharmacokinetic parameters were determined. 2HF demonstrated a C of 185.86 ng/mL, a T of 5 min, and a half-life (T) of 97.52 min.
由于缺乏投资、结构以及代谢物分离的困难，有前景的天然产物研究无法推进到临床前研究，如药代动力学研究。2'-羟基黄烷酮（2HF）是一种黄酮类化合物，已在不同类型的癌症和利什曼病研究中显示出有前景的结果。为了准确测定BALB/c小鼠血液中的2HF，开发了一种经过验证的高效液相色谱-串联质谱（HPLC-MS/MS）方法。色谱分析使用C（5μm，150mm×4.6mm）进行。流动相由含有0.1%甲酸的水、乙腈和甲醇（35/52/13 v/v/v）组成，流速为0.8mL/min，总运行时间为5.50min，进样体积为20µL。采用电喷雾电离负离子模式（ESI-）和多反应监测（MRM）检测2HF。经过验证的生物分析方法显示出令人满意的选择性，对2HF和内标物无明显干扰。此外，1至250ng/mL的浓度范围显示出良好的线性（r = 0.9969）。该方法在基质效应方面显示出令人满意的结果。精密度和准确度区间分别在1.89%至6.76%以及95.27%至100.77%之间，符合标准。由于在冻融条件下、短时间、后处理和长时间条件下的稳定性偏差均小于15%，因此未观察到生物基质中2HF的降解。该方法经验证后成功应用于小鼠血液中2HF的口服药代动力学研究，并测定了药代动力学参数。2HF的C为185.86ng/mL，T为5min，半衰期（T）为97.52min。
