维库溴铵,罗库溴铵,和潘库溴铵被广泛用作非去极化肌肉松弛剂。使用这种肌肉松弛剂时,偶尔会出现过敏反应甚至死亡的情况。快速测定血液中这些肌松药的浓度可以为早期临床诊断提供有价值的信息。作为季铵化合物,这些肌肉松弛剂是高度极性的。因此,它们不能有效地保留在具有常规流动相的反相色谱柱上。这些季铵肌肉松弛剂主要通过离子对色谱法分离。使用离子配对试剂可以帮助提高季铵肌肉松弛剂的保留能力。然而,由于流动相中离子配对试剂引起的离子抑制,MS检测的灵敏度显着降低。此外,离子配对试剂会污染MS系统。建立了高效液相色谱-串联质谱(HPLC-MS/MS)同时测定血液中3种季铵盐类肌松药含量的方法。稀释血液样品并进行高速离心。上清液在BondElutAL-N固相萃取柱上纯化,然后通过0.45μm微孔膜过滤。季铵肌肉松弛剂在ZIC-cHILIC分析柱上分离(50mm×2.1mm,3.0μm),梯度洗脱。乙腈和0.1%甲酸水溶液用作流动相。通过串联MS与电喷雾电离(ESI)源在正和多反应监测(MRM)模式下分析分离的化合物。维库溴铵的基质效应,罗库溴铵,血中潘库溴铵占88.1%~95.4%。维库溴铵的校准曲线,罗库溴铵,和潘库溴铵在每个范围内都表现出良好的线性关系,所有相关系数(R2)均>0.996。维库溴铵的检测限,罗库溴铵,潘库溴铵为0.2-0.8ng/mL,相应的定量限为0.5-2.0ng/mL。维库溴铵的回收率,罗库溴铵,潘库溴铵占92.8%至110.6%,相对标准偏差(RSD)为3.2%-9.4%。这个方法很灵敏,准确,易于操作,它可以用来快速测定维库溴铵,罗库溴铵,和血中的潘库溴铵.
Vecuronium, rocuronium, and
pancuronium are widely used as non-depolarizing muscle relaxants. There have been occasional cases of allergic reactions and even death when using such muscle relaxants. Rapid determination of the concentration of these muscle relaxants in blood can provide valuable information for early clinical diagnosis. As quaternary ammonium compounds, these muscle relaxants are highly polar. Hence, they cannot be retained effectively on reversed-phase chromatographic columns with conventional mobile phases. These quaternary ammonium muscle relaxants are mainly separated by ion-pair chromatography. Using an ion-pairing reagent can help improve the retention capabilities of quaternary ammonium muscle relaxants. Nevertheless, the sensitivity of MS detection is significantly decreased because of ionic inhibition caused by the ion-pairing reagent in the mobile phase. Furthermore, ion-pairing reagents can pollute the MS system. A method based on high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was established for the simultaneous determination of the three quaternary ammonium muscle relaxants in blood. The blood samples were diluted and subjected to high-speed centrifugation. The supernatant was purified on a Bond Elut AL-N solid phase extraction column and then filtered through a 0.45 μm microporous membrane. The quaternary ammonium muscle relaxants were separated on a ZIC-cHILIC analytical column (50 mm×2.1 mm, 3.0 μm) with gradient elution. Acetonitrile and 0.1% formic acid aqueous solution were used as mobile phases. The separated compounds were analyzed by tandem MS with an electrospray ionization (ESI) source in positive and multiple reaction monitoring (MRM) modes. The matrix effects of vecuronium, rocuronium, and
pancuronium in blood were 88.1% to 95.4%. The calibration curves for vecuronium, rocuronium, and
pancuronium showed good linear relationships in each range, and all correlation coefficients (R2) were > 0.996. The limits of detection of vecuronium, rocuronium, and
pancuronium were 0.2-0.8 ng/mL, with the corresponding limits of quantification being 0.5-2.0 ng/mL. The recoveries of vecuronium, rocuronium, and
pancuronium were 92.8% to 110.6%, with relative standard deviations (RSDs) of 3.2%-9.4%. This method is sensitive, accurate, and easy to operate, and it can be used to rapidly determine vecuronium, rocuronium, and pancuronium in blood.