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通过 LC-MS/MS 同时测定紫杉醇和硼替佐米:药物和药代动力学应用。

Simultaneous estimation of paclitaxel and bortezomib via LC-MS/MS: pharmaceutical and pharmacokinetic applications.

机构信息

Division of Pharmaceutics & Pharmacokinetics, CSIR-Central Drug Research Institute, Lucknow, 226031, UP, India.

Academy of Scientific & Innovative Research (AcSIR), Ghaziabad, 201002, India.

出版信息

Nanomedicine (Lond). 2024;19(24):1995-2010. doi: 10.1080/17435889.2024.2382668. Epub 2024 Aug 8.

Abstract

This study evaluates the potential of combining paclitaxel (PTX) and bortezomib (BTZ) for breast cancer therapy. The nanoformulation was optimized via Box-Behnken Design (BBD), with method validation adhering to US-FDA guidelines. Multiple reaction monitoring transitions for PTX, BTZ and internal standard were m/z 855.80→286.60, 366.80→226.00 and 179.80→110.00, respectively. Elution done on C18 Luna column with 0.1% FA in MeOH:10 mM ammonium acetate. The size of nanoformulation was 133.9 ± 1.97 nm, PDI 0.19 ± 0.01 and zeta potential -19.20 ± 1.36 mV. Pharmacokinetics showed higher C for PTX-BTZ-NE (313.75 ± 10.71 ng/ml PTX, 11.92 ± 0.53 ng/ml BTZ) versus free PTX-BTZ (104 ± 13.06 ng/ml PTX, 1.9 ± 0.08 ng/ml BTZ). Future findings will contribute to the treatment of breast cancer using PTX and BTZ.

摘要

这项研究评估了紫杉醇(PTX)和硼替佐米(BTZ)联合用于乳腺癌治疗的潜力。采用 Box-Behnken 设计(BBD)对纳米制剂进行了优化,方法验证符合美国 FDA 指南。PTX、BTZ 和内标物的多重反应监测转换为 m/z 855.80→286.60、366.80→226.00 和 179.80→110.00。在 C18 Luna 柱上用 0.1% FA 在 MeOH:10 mM 乙酸铵洗脱。纳米制剂的粒径为 133.9±1.97nm,PDI 为 0.19±0.01,zeta 电位为-19.20±1.36mV。药代动力学研究表明,PTX-BTZ-NE(PTX 为 313.75±10.71ng/ml,BTZ 为 11.92±0.53ng/ml)的 C 明显高于游离的 PTX-BTZ(PTX 为 104±13.06ng/ml,BTZ 为 1.9±0.08ng/ml)。未来的研究结果将有助于使用 PTX 和 BTZ 治疗乳腺癌。

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