Chihoho B, Sage A B, Smolenski R T, Vazir A, Rose M L, Banner N R, Leaver N V
Royal Brompton and Harefield NHS Foundation Trust, Harefield, Middlesex, UK.
Biomed Chromatogr. 2012 May;26(5):566-70. doi: 10.1002/bmc.1675. Epub 2011 Sep 8.
Milrinone is a bipyridine phosphodiesterase inhibitor with positive inotropic and vasodilatory effects. As interest in longer term use of intravenous therapy increases, it becomes essential to monitor its plasma concentration owing to a narrow therapeutic range, an increased half-life in renal failure and toxicity associated with high levels. A high-performance liquid chromatography (HPLC) method with mass (MS) detection using a triple quadrupole mass spectrometer is presented. The method was compared with the UV/HPLC method and validated according to current international guidelines. Coefficients of variation of less than 7.5% were obtained across the therapeutic range and 18.3% at 2.4 ng/mL, the lower limit of quantitation. Plasma from 13 cardiac surgery patients receiving standard intravenous doses of milrinone were measured. Eight patients achieved therapeutic milrinone levels within 3-4 h post start of infusion, one was borderline sub-therapeutic and four patients achieved levels that were above the upper limit of the therapeutic range and potentially toxic. This method offers high sensitivity, is rapid, easy to use and requires minimal amount of sample. We believe this method could become the reference procedure for clinical monitoring of milrinone and help to improve the safety of the use of this drug in patients with cardiac failure.
米力农是一种具有正性肌力和血管舒张作用的双吡啶磷酸二酯酶抑制剂。随着对静脉治疗长期使用的兴趣增加，由于其治疗窗狭窄、肾衰竭时半衰期延长以及与高浓度相关的毒性，监测其血浆浓度变得至关重要。本文介绍了一种使用三重四极杆质谱仪进行质量（MS）检测的高效液相色谱（HPLC）方法。该方法与紫外/高效液相色谱法进行了比较，并根据现行国际指南进行了验证。在整个治疗范围内变异系数小于7.5%，在定量下限2.4 ng/mL时为18.3%。对13例接受标准静脉剂量米力农的心脏手术患者的血浆进行了检测。8例患者在输注开始后3 - 4小时内达到米力农治疗水平，1例接近亚治疗水平，4例患者达到高于治疗范围上限且可能有毒的水平。该方法灵敏度高、快速、易于使用且所需样品量最少。我们认为该方法可成为米力农临床监测的参考方法，并有助于提高心力衰竭患者使用该药物的安全性。
