目的 建立应用LC-MS/MS进行大鼠血浆、尿液、结肠中美沙拉嗪及其体内代谢物N-乙酰-5-ASA浓度的测定方法,并将其应用于美沙拉嗪及N-乙酰-5-ASA在大鼠体内过程的研究。方法 血浆、尿液及结肠样品均用甲醇沉淀蛋白进行提取,以ESI电离源在负离子模式下检测,用Agilent HC-C18色谱柱,甲醇-醋酸水溶液为流动相梯度洗脱,流速为1.0 mL·min-1。结果 美沙拉嗪及N-乙酰-5-ASA在大鼠血浆、尿液及结肠中的线性范围及定量限均符合测定要求,日内、日间精密度及基质效应均 < 15%。结论 本方法快速、灵敏、专属性强且重现性好,可用于大鼠血浆、尿液、结肠中美沙拉嗪及N-乙酰-5-ASA测定。
Abstract
OBJECTIVE To develop an LC-MS/MS method for determination of mesalazine and its metabolite, N-Ac-5-ASA, in rat plasma, urine and colon for the pharmacokinetic study of mesalazine and N-Ac-5-ASA in rats. METHODS The plasma, urine and colon samples were treated with methanol to precipitate protein. An Agilent HC-C18 column was used as the analytical column, with methanol and acetic acid aqueous solution as mobile phase eluted by a gradient program at a flow rate of 1.0 mL穖in-1. The detection was accomplished with ESI source operated in negative ionization mode. RESULTS The linearity and LLOQs of mesalazine and N-Ac-5-ASA in rat plasma, urine and colon both met the requirements, and the inter- and intra-day RSDs and matrix effect were less than 15%. CONCLUSION This assay is a rapid, sensitive, selective and reliable method for determination of mesalazine and N-Ac-5-ASA in rat plasma, urine and colon.
关键词
高效液相色谱-质谱联用 /
美沙拉嗪 /
N-乙酰-5-ASA
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Key words
LC-MS/MS /
mesalazine /
N-Ac-5-ASA
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中图分类号:
R917
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参考文献
DOROFEYEV A E, KIRIYAN E A, VASILENKO I V, et al. Clinical, endoscopical and morphological efficacy of mesalazine in patients with irritable bowel syndrome . Clin Exp Gastroenterol, 2011, 4: 141-153. PASTORINI E, LOCATELLI M, SIMONI P, et al. Development and validation of a HPLC-ESI-MS/MS method for the determination of 5-aminosalicylic acid and its major metabolite N-acetyl-5-aminosalicylic acid in human plasma . J Chromatogr B, 2008, 872 (1-2): 99-106. NOBILIS M, VYBIRALOVA Z, SLADKOVA K, et al. High-performance liquid-chromatographic determination of 5-aminosalicylic acid and its metabolites in blood plasma . J Chromatogr A, 2006, 1119 (1-2): 299-308. GANDIA P, IDIER I, HOUIN G. Is once-daily mesalazine equivalent to the currently used twice-daily regimen A study performed in 30 healthy volunteers . J Clin Pharmacol, 2007, 47 (3): 334-342. PALUMBO G, BACCHI S, PRIMAVERA L, et al. A validated HPLC method with electrochemical detection for simultaneous assay of 5-aminosalicylic acid and its metabolite in human plasma . Biomed Chromatogr, 2005, 19 (5): 350-354.
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脚注
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