Salem Alaa A, Wasfi Ibrahim, Al-Nassib Salama S, Allawy Mohsin Mahmoud, Al-Katheeri Nawal
Department of Chemistry, College of Science, United Arab Emirates University, AlAin, PO Box 15551, United Arab Emirates.
Forensic Evidence Department, Abu Dhabi, PO Box 253, United Arab Emirates.
J Chromatogr Sci. 2017 Sep 1;55(8):846-856. doi: 10.1093/chromsci/bmx045.
A highly sensitive method for the determinations of acebutolol, clenbuterol, nadolol, oxprenolol, propranolol, terbutaline and timolol β-blockers and β2-agonists in plasma and urine was developed. The method was optimized using electrospray ionization liquid chromatography-tandem mass spectrometry (LC-ESI-MS-MS) and clean screen solid phase extraction cartridges. Matrix effect was reduced by removing co-extractives from the SPE cartridges using methanol prior to drugs' elution. Using blood and serum matrices for calibration and applying the internal standard method has also contributed to the reduction of matrix effect. Method's validation yielded linear dynamic ranges of 5.0-50.0 and 50.0-1000.0 ng/ml for drugs spiked in plasma and urine respectively. It also gave correlation coefficients of 0.94-0.99, detection limits ranged in 0.06-5.04 pg/ml and quantification limits ranged in 0.14-22.88 pg/ml for the target drugs. Developed method was successfully applied to the analysis of β-blockers and β2-agonists in plasma and urine samples. Plasma samples fortified with drugs at 7.5, 40.0 and 75.0 ng/ml gave percentage recoveries ranged in 78.66-118.10, 67.02-83.97 and 74.77-93.80, respectively. Urine samples fortified with drugs at 80.0, 400.0 and 800.0 ng/ml gave percentage recoveries ranged in 104.68-130.18, 110.23-125.16 and 109.46-116.89, respectively. Variance coefficients ranged in 0.05-0.35 and 0.04-0.12 were, respectively, obtained for the analyses of drugs in plasma and urine samples. Results suggest that developed method is well suited for the analysis of investigated drugs in biological fluids.
建立了一种高灵敏度的方法，用于测定血浆和尿液中的醋丁洛尔、克伦特罗、纳多洛尔、氧烯洛尔、普萘洛尔、特布他林和噻吗洛尔等β受体阻滞剂和β2激动剂。该方法采用电喷雾电离液相色谱-串联质谱法（LC-ESI-MS-MS）和Clean Screen固相萃取柱进行优化。在药物洗脱前，先用甲醇从固相萃取柱中去除共提取物，以降低基质效应。使用血液和血清基质进行校准并应用内标法也有助于降低基质效应。方法验证得出，血浆和尿液中加标药物的线性动态范围分别为5.0 - 50.0 ng/ml和50.0 - 1000.0 ng/ml。目标药物的相关系数为0.94 - 0.99，检测限在0.06 - 5.04 pg/ml范围内，定量限在0.14 - 22.88 pg/ml范围内。所建立的方法成功应用于血浆和尿液样本中β受体阻滞剂和β2激动剂的分析。血浆样本中分别加入7.5、40.0和75.0 ng/ml的药物，回收率分别在78.66 - 118.10、67.02 - 83.97和74.77 - 93.80范围内。尿液样本中分别加入80.0、400.0和800.0 ng/ml的药物，回收率分别在104.68 - 130.18、110.23 - 125.16和109.46 - 116.89范围内。血浆和尿液样本中药物分析的变异系数分别在0.05 - 0.35和0.04 - 0.12范围内。结果表明，所建立的方法非常适合分析生物体液中的被测药物。
