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目的:建立灵敏的超高效液相色谱-质谱联用法测定比格犬血浆中的阿司匹林、水杨酸和单硝酸异山梨酯的浓度。方法:选用Waters BEH C18(100 mm×2.1 mm,1.7μm)色谱柱,分别以0.5%甲酸/5 mmol.L-1醋酸铵-乙腈和2 mmol.L-1醋酸铵-乙腈为流动相,采用梯度洗脱进行分离,样品采用乙酸乙酯提取后进样,通过电喷雾电离源,以多重反应监测(MRM)方式进行负离子检测,用于定量分析的离子对分别为m/z 178.9→136.9(阿司匹林)、m/z 136.9→64.9(水杨酸)和m/z 293.7→250.0(内标,双氯酚酸钠)测定阿司匹林和水杨酸;m/z 249.6→58.9(单硝酸异山梨酯)和m/z 293.7→250.0(内标,双氯酚酸钠)测定单硝酸异山梨酯。结果:阿司匹林、水杨酸和单硝酸异山梨酯的线性范围分别为2.0～2000.0,20.0～16000.0,9.6～9557.0 ng.mL-1;定量下限分别可达2.0,20.0,9.6 ng.mL-1;日内、日间精密度(RSD)均小于15%。结论:本方法灵敏度较高,血浆用量少,适用于比格犬血浆样品中阿司匹林、水杨酸和单硝酸异山梨酯的测定和药物动力学研究。
OBJECTIVE: To establish a sensitive ultra-performance liquid chromatography-mass spectrometry method for the determination of aspirin, salicylic acid and isosorbide mononitrate in beagle dogs plasma. Methods: Waters BEH C18 (100 mm × 2.1 mm, 1.7 μm) was used as mobile phase with 0.5% formic acid / 5 mmol·L-1 ammonium acetate-acetonitrile and 2 mmol·L-1 ammonium acetate- Gradient elution was used to separate the samples. The samples were extracted with ethyl acetate and injected into the sample. Electrospray ionization (ESI) ionization was used to detect negative ions by multiple reaction monitoring (MRM). The ion pairs for quantitative analysis were m / z 178.9 → 136.9 (Aspirin), aspirin and salicylic acid at m / z 136.9 → 64.9 (salicylic acid) and m / z 293.7 → 250.0 (internal standard, diclofenac sodium); m / z 249.6 → 58.9 (isosorbide mononitrate Ester) and m / z 293.7? 250.0 (internal standard, diclofenac sodium) were measured for isosorbide mononitrate. Results: The linear ranges of aspirin, salicylic acid and isosorbide mononitrate were 2.0 ~ 2000.0, 20.0 ~ 16000.0 and 9.6 ~ 9557.0 ng.mL-1, respectively. The lower limit of quantitation was 2.0, 20.0 and 9.6 ng.mL-1 ; Day, day precision (RSD) were less than 15%. Conclusion: This method has high sensitivity and low plasma dosage, and is suitable for the determination and pharmacokinetics of aspirin, salicylic acid and isosorbide mononitrate in Beagle dog plasma samples.