LC-ESI-MS 测定新的抗胆碱能化合物苯环喹溴铵在大鼠胆汁、尿液和粪便中的含量

中国临床药理学与治疗学 ›› 2007, Vol. 12 ›› Issue (4): 385-391.

LC-ESI-MS 测定新的抗胆碱能化合物苯环喹溴铵在大鼠胆汁、尿液和粪便中的含量

徐勤¹, 丁黎¹, 刘文英¹, 陈小平², 李荣姗¹, 宋沁馨¹

¹中国药科大学药物分析教研室, 南京210009, 江苏;
²北京世桥生物技术有限公司, 北京100080

收稿日期:2007-03-08 修回日期:2007-03-08 发布日期:2020-10-30
作者简介:徐勤, 女, 在读博士生, 副教授, 研究方向:药物分析。Tel:13977327933 E-mail:xuqincpu @yahoo.com.cn

Determination of bencycloquidium bromide, a novel anticholinergic compound,in rat’ s bile, urine and feces by LC-ESI-MS

XU Qin¹, DINg/Li¹, LIU Wen-ying¹, CHEN Xiao-ping², LI Rong-shan¹, SONG Qin-xin¹

¹Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing 210009, Jiangsu, China;
²Beijing Shiqiao Biological and Pharmaceutical Co.Ltd., Haidian Area, Beijing 100080, China

Received:2007-03-08 Revised:2007-03-08 Published:2020-10-30

摘要/Abstract

摘要： 目的首次建立了LC-ESI-MS 法测定大鼠胆汁、尿液和粪便中苯环喹溴铵的浓度, 对该药在大鼠体内的排泄规律进行研究, 为该药在大鼠体内的代谢转化途径的研究和临床试验提供依据。方法生物样品经过C18固相小柱提取后, 采用LC-ESI-MS 法进行测定。以1-乙基-苯环喹溴铵为内标, 在Hanbon Lichrospher 5-C₁₈色谱柱上, 甲醇-(含40 mmol L 醋酸铵和1 %甲酸) 水溶液(70:30, v v) 为流动相, 流速为0.8 mL min 分析胆汁样品;甲醇-(含40 mmol L 醋酸铵和1 %甲酸) 水溶液(75:25, v v) 为流动相, 流速为1.0 mL min 分析尿液、粪便样品;以气动辅助电喷雾离子化(ESI) 为接口技术, 选择性正离子监测方式,苯环喹溴铵的分子离子([M] +m z 330.2) 和内标1-乙基-苯环喹溴铵的分子离子([M] + m z 344.2) 作为测定离子。结果胆汁、尿样、粪便中苯环喹溴铵的回收率均大于77 %, 日间和日内的变异系数均小于15 %。胆汁中苯环喹溴铵在30.15 ~1507.50 ng mL 浓度范围内线性关系良好(r =0.9995), 最低定量限为30.15 ng mL 。尿液中苯环喹溴铵在3.02 ~ 1507.50 ng mL 浓度范围内线性关系良好(r =0.9997), 最低定量限为3.02 ng mL 。粪便中苯环喹溴铵在3.02 ~ 1507.50 ng mL 浓度范围内线性关系良好(r =0.9995), 最低定量限为3.02 ng mL。结论该方法专属性强, 准确可靠, 灵敏度高, 可满足大鼠鼻腔给药排泄研究中药物浓度测定的要求。

关键词: 苯环喹溴铵, 胆汁, 尿液, 粪便, 排泄, LCESI-MS 法

Abstract: AIM: This study was undertaken to study the excretion rule of bencycloquidium bromide (BCQB) in rats, and a LC-ESI-MS method was developed for the determination of BCQB in bile, urine and feces sample of rats. METHODS: A liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) assay for the determination of BCQB in rats bile, urine and feces was firstly developed and validated.After addition of 1-ethyl-bencycloquidium bromide as an internal standard (I.S.), the biological samples were prepared by using solid phase extraction on a C18-cartridge column.Chromatographic separation was analyzed on a Hanbon Lichrospher 5-C18 column.The mobile phase consisted of methanol-40 mmol L ammonium acetate buffer-formic acid (70:30: 0.3, v v v) was pumped at 0.8 mL min for bile.The mobile phase consisted of methanol-40mmol L ammonium acetate buffer-formic acid (75:25:0.25, v v v) was pumped at 1.0 mL min for urine and feces.LC-ESI-MS was carried out on a single quadrupole mass spectrometer using electrospray ionization (ESI) and positive selectedion monitoring (SIM).Target ions were monitored at [M] + m z 330.2 for BCQB and [M] +m z 344.2 for I. S.. RESULTS: The extraction recoveries of BCQB in bile, urine and feces were upper 77 %.The RSD of intrarun and inter-run precisions were all below 15 %.The calibration curves were linear over the concentration ranges of 30.15-1507.50 ng mL (r =0.9995) for the BCQB in bile, and the low limit of quantitative (LLOQ) was 30.15 ng mL.The calibration curves were linear over the concentration ranges of 3.02-1507.50 ng mL (r = 0.9997) for the BCQB in urine, and the LLOQ was 3.02 ng mL.The calibration curves were linear over the concentration ranges of 3.02-1507.50 ng mL (r =0.9997) for the BCQB in feces, and the LLOQ was 3.02 ng mL. CONCLUSION: The method is specific, accurate, reliable and sensitive.The established method has successfully been applied to study the excretion of BCQB in rats after intranasal administration.

Key words: bencycloquidium bromide, bile, urine, feces, excretion, LC-ESI-MS

中图分类号:

R969.1

徐勤, 丁黎, 刘文英, 陈小平, 李荣姗, 宋沁馨. LC-ESI-MS 测定新的抗胆碱能化合物苯环喹溴铵在大鼠胆汁、尿液和粪便中的含量[J]. 中国临床药理学与治疗学, 2007, 12(4): 385-391.

XU Qin, DINg/Li, LIU Wen-ying, CHEN Xiao-ping, LI Rong-shan, SONG Qin-xin. Determination of bencycloquidium bromide, a novel anticholinergic compound,in rat’ s bile, urine and feces by LC-ESI-MS[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2007, 12(4): 385-391.

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