Page 64 - 《中国药科大学学报》2025年第4期

学报
460 Journal of China Pharmaceutical University 2025, 56(4): 460 − 468

基于药代动力学的甲钴胺与头孢曲松钠

大鼠体内药物相互作用研究

王呈鑫，朱莉莉，曹丽娟 *

（中国药科大学多靶标天然药物全国重点实验室, 南京 210009）

摘 要 本研究建立大鼠血浆中甲钴胺及头孢曲松钠 LC-MS/MS 定量检测方法，通过该方法评估两药在大鼠体内的药代动
力学行为，进而评判二者是否存在基于药代动力学的药物相互作用。实验以甲醇作为蛋白沉淀剂处理大鼠血浆样本，甲钴胺
定量分析的流动相由 0.1% 甲酸乙腈与 0.1% 甲酸和 2 mmol/L 乙酸铵水溶液组成；头孢曲松钠则为 0.1% 甲酸乙腈和 1% 甲
酸水溶液。基于正离子模式，分别建立两药的 LC-MS/MS 定量分析方法，并开展全面的方法学考证。选用健康 SD 大鼠进行
药代动力学研究，经尾静脉注射进行单次单独给药与单次联合给药实验。甲钴胺的给药剂量梯度设为 0.03、0.1 和
0.3 mg/kg，头孢曲松钠的给药剂量设为 90 mg/kg。方法学验证结果表明，甲钴胺在 3~3 000 ng/mL 范围内线性关系良好
(r=0.999 1) ，头孢曲松钠在 0.5~500 μg/mL 范围内线性关系优异 (r=1) ，两种药物分析方法的选择性、精密度、准确度、提取回
收率、基质效应和稳定性均符合生物分析方法验证要求。药代动力学研究显示，与单次单独给药相比，单次联合给药时两药
的平均药时曲线重合，主要药代动力学参数（如 t 1/2 , AUC 0-∞ 等）经单因素方差分析无显著性差异（P＞0.05）。研究证实，
甲钴胺与头孢曲松钠的联合使用时，在大鼠体内不存在基于药代动力学的药物相互作用，本研究为临床两药的联用提供了可
靠的药代动力学依据。
关键词 甲钴胺；头孢曲松钠；药代动力学；药物相互作用；LC-MS/MS
中图分类号 R965 文献标志码 A 文章编号 1000−5048(2025)04−0460−09
doi：10.11665/j.issn.1000−5048.2025022101

引用本文 王呈鑫，朱莉莉，曹丽娟. 基于药代动力学的甲钴胺与头孢曲松钠大鼠体内药物相互作用研究 [J]. 中国药科大学学报，2025，
56（4）：460 − 468.

Cite this article as: WANG Chengxin, ZHU Lili, CAO Lijuan. Research on the drug-drug interaction between mecobalamin and ceftriaxone in
rats based on pharmacokinetics[J]. J China Pharm Univ, 2025, 56(4): 460 − 468.

Research on the drug-drug interaction between mecobalamin and ceftriaxone
in rats based on pharmacokinetics
WANG Chengxin, ZHU Lili, CAO Lijuan *
State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China

Abstract LC-MS/MS methods for the quantitative determination of mecobalamin and ceftriaxone in rat plasma
were established, and utilized to assess the pharmacokinetic behaviors of the two drugs in rats and to determine
whether there were pharmacokinetics-based drug-drug interactions between them. Methanol was used as a protein
precipitant to process rat plasma samples. For mecobalamin, acetonitrile containing 0.1% formic acid was used as
the organic phase, while an aqueous solution of 0.1% formic acid and 2 mmol/L ammonium acetate served as the
aqueous phase. For ceftriaxone, the organic phase was acetonitrile with 0.1% formic acid, and the aqueous phase
was a 1% formic acid aqueous solution. LC-MS/MS quantitative analysis methods for both drugs were developed
under the positive ion mode, followed by comprehensive methodological validation. Single-dose administration
(either alone or in combination) was carried out via caudal vein injection. The dosing regimens were 0.03, 0.1,
and 0.3 mg/kg for mecobalamin and 90 mg/kg for ceftriaxone. The results of methodological validation indicated

收稿日期 2025-02-21 * 通信作者 Tel：15950496613 E-mail：caolijuan0702@cpu.edu.cn