School of Pharmacy, China Medical University, Shenyang 110122, China.
School of Pharmacy, Hainan Medical University, Haikou 570100, China.
Molecules. 2024 Jun 4;29(11):2652. doi: 10.3390/molecules29112652.
Itampolin A, a natural brominated tyrosine alkaloid isolated from the sponge , has been shown to have good inhibitory effects in lung cancer cells as a p38α inhibitor. A simple, sensitive, and reliable ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method has been established, validated, and applied to the study of the pharmacokinetics and tissue distribution of itampolin A following intragastric and intravenous administration. Itampolin A and theophylline (internal standard, IS) were extracted by the simple protein precipitation technique using methanol as the precipitating solvent. Chromatographic separation was achieved by using the optimized mobile phase of a 0.1% formic acid aqueous solution and acetonitrile in the gradient elution mode. Itampolin A and IS were detected and quantified using positive electrospray ionization in the multiple reaction monitoring mode with transitions of / 863.9 → 569.1 for itampolin A and / 181.1 → 124.1 for IS, respectively. The assay exhibited a linear dynamic range of 1-1600 ng/mL for itampolin A in biological samples and the low limit of quantification was 1 ng/mL. Non-compartmental pharmacokinetic parameters indicated that itampolin A was well-absorbed into the systemic circulation and rapidly eliminated after administration. The apparent distribution volume of itampolin A was much higher after intragastric administration than that after intravenous administration. A tissue distribution study showed that itampolin A could be detected in different tissues and maintained a high concentration in the lung, which provided a material basis for its effective application in lung cancer. The pharmacokinetic process and tissue distribution characteristics of imtapolin A were expounded in this study, which can provide beneficial information for the further research and clinical application of itampolin A.
坦波林 A 是从海绵中分离出来的天然溴代酪氨酸生物碱，作为 p38α 抑制剂，在肺癌细胞中显示出良好的抑制作用。建立了一种简单、灵敏、可靠的超高效液相色谱-串联质谱（UHPLC-MS/MS）方法，并对坦波林 A 灌胃和静脉给药后的药代动力学和组织分布进行了研究。坦波林 A 和茶碱（内标，IS）采用简单的蛋白质沉淀技术，以甲醇作为沉淀溶剂提取。采用优化的流动相，0.1%甲酸水溶液和乙腈梯度洗脱模式进行色谱分离。采用正电喷雾电离，多反应监测模式，坦波林 A 的监测离子对为 863.9→569.1，内标的监测离子对为 181.1→124.1，对坦波林 A 和 IS 进行检测和定量。坦波林 A 在生物样品中的线性动态范围为 1-1600ng/mL，定量下限为 1ng/mL。非房室药代动力学参数表明，坦波林 A 经灌胃给药后能很好地被吸收进入体循环，并在给药后迅速消除。坦波林 A 经灌胃给药后的表观分布容积明显高于静脉给药后。组织分布研究表明，坦波林 A 可在不同组织中检测到，并在肺部保持高浓度，这为其在肺癌中的有效应用提供了物质基础。本研究阐述了坦波林 A 的药代动力学过程和组织分布特征，可为坦波林 A 的进一步研究和临床应用提供有益信息。
