摘要
目的建立同时测定比格犬血浆中美托拉宗和缬沙坦的高效液相色谱串联质谱法。方法分析柱为Agilent Poroshell 120色谱柱（2.1 mm×30 mm×2.7μm）。质谱采用电喷雾离子源（ESI）,采用多反应监测（MRM）,检测离子为正离子,分别选择m/z 366.2/259、436.2/291和423.4/207作为美托拉宗、缬沙坦和内标（氯沙坦钾）的检测离子对。结果美托拉宗、缬沙坦的线性范围分别为0.5-100及5-5000 ng/ml,相关系数r^2分别为0.9937和0.9939,批内精密度分别为2.09%-8.85%和2.36%-13.12%,基质效应分别为87.73%-98.62%和99.03%-137.35%,回收率分别为75.74%-81.82%和83.89%-95.64%。结论该法操作简单、准确可靠、检测灵敏度高,可用于复方美托拉宗缬沙坦速释片比格犬体内的药代动力学研究。
Objective To develop an LC-MS/MS method for simultaneous determination of metolazone and valsartan in beagle dog plasma. Methods The chromatographic separation was achieved on an Agilent Poroshell 120（ 2. 1 mm × 30 mm ×2. 7 μm） analytical column. The multiple reaction monitoring mode operating in positive ion was adopted in MS detection,and precursors to the product ion transitions of m / z 366. 2 /259,436. 2 /291 and 423. 4 /207 were used to measure metolazone,valsartan and internal standard（ losartan potassium）. Results The method was linear over the concentration range of0. 5 ng / ml- 100 ng / ml for metolazone and 5- 5000 ng / ml for valsartan,with the correlation coefficients（ r^2） of 0. 9937 and 0. 9939,respectively. The average intra-day precision values（ RSD） were 2. 09%- 8. 85% for metolazone and2. 36%- 13. 12% for valsartan. The matrix effect values were 87. 73%- 98. 62% for metolazone and 99. 03%- 137. 35%for valsartan. The average recovery was 75. 74%- 81. 82% for metolazone and 83. 89%- 95. 64% for valsartan. Conclusion This analytical method for metolazone and valsartan is simple,accurate and sensitive,so it can be used for pharmacokinetic research of metolazone and valsartan immediate release tablets in beagle dogs.
出处
《军事医学》
CAS
CSCD
北大核心
2016年第4期346-349,共4页
Military Medical Sciences
