Laboratory of Pharmaceutical Analysis, Department of Pharmaceutical Technology, School of Pharmacy, Aristotle University of Thessaloniki, 54124, Thessaloniki, Greece.
Department of Chemistry and Biochemistry, International Forensic Research Institute, Florida International University, Miami, FL, 33131, USA.
Mikrochim Acta. 2023 Oct 5;190(11):428. doi: 10.1007/s00604-023-05998-3.
A sol-gel Carbowax 20 M/3-[(3-Cholamidopropyl) dimethyl ammonio]-1-propanesulfonate composite sorbent-based capsule phase microextraction device has been fabricated and characterized for the determination of four statins (pravastatin, rosuvastatin, pitavastatin, and atorvastatin) in human urine. The presence of ionizable carboxyl functional groups in statins requires pH adjustment of the sample matrix to ensure that the target molecules are in their protonated form (pH should be 2 units below their pK values) which not only is cumbersome but also risks unintended contamination of the sample. This challenge was addressed by introducing zwitterionic ionic liquid in addition to neutral, polar Carbowax 20 M polymer in the sol-gel-derived composite sorbent. As such, the composite zwitterionic multi-modal sorbent can simultaneously extract neutral, cationic, and anionic species. This particular attribute of the composite sorbent eliminates the necessity of the matrix pH adjustment and consequently simplifies the overall sample preparation workflow. Various experimental parameters such as the sample amount, extraction time, salt addition, stirring rate, and elution solvent type that may affect the extraction performance of the statins were investigated using a central composite design and the one-parameter-at-a-time approach. The analytes and the internal standard were separated on a Ccolumn with gradient elution using phosphate buffer (20 mM, pH 3) and acetonitrile as mobile phase. The analytes were detected at 237 nm. The method was validated, and linearity was observed in the range 0.10-2.0 μg mL for all compounds. The method precision was better 9.9% and 10.4% for intra-day and inter-day, respectively, while the relative recoveries were acceptable, ranging between 83.4 and 116% in all cases. Method greenness was assessed using the ComplexGAPI index. Finally, the method's applicability was demonstrated in the determination of the statins in authentic human urine after oral administration of pitavastatin and rosuvastatin-containing tablets.
一种基于溶胶-凝胶 Carbowax 20 M/3-[(3-胆酰胺丙基)二甲氨基]-1-丙磺酸钠复合吸附剂的胶囊相微萃取装置已被制备和表征，用于测定人尿中的四种他汀类药物（普伐他汀、罗苏伐他汀、匹伐他汀和阿托伐他汀）。他汀类药物中存在可电离的羧基官能团，需要调整样品基质的 pH 值，以确保目标分子处于质子化形式（pH 值应比其 pK 值低 2 个单位），这不仅繁琐，而且还存在样品意外污染的风险。为了解决这一挑战，除了中性、极性的 Carbowax 20 M 聚合物外，还在溶胶-凝胶衍生的复合吸附剂中引入了两性离子离子液体。因此，复合两性离子多模态吸附剂可以同时提取中性、阳离子和阴离子物质。这种复合吸附剂的特殊属性消除了对基质 pH 值调整的必要性，从而简化了整个样品制备工作流程。通过中心复合设计和单参数逐一改变的方法，研究了样品量、萃取时间、加盐量、搅拌速度和洗脱溶剂类型等各种实验参数，这些参数可能会影响他汀类药物的萃取性能。使用磷酸盐缓冲液（20 mM，pH 3）和乙腈作为流动相，在 C 柱上进行梯度洗脱，分离分析物和内标。在 237nm 处检测分析物。该方法经过验证，所有化合物的线性范围均为 0.10-2.0μgmL。日内和日间精密度分别为 9.9%和 10.4%，相对回收率在所有情况下均为可接受的 83.4%至 116%。使用 ComplexGAPI 指数评估方法的绿色度。最后，该方法在口服含有匹伐他汀和罗苏伐他汀的片剂后测定人尿中他汀类药物的实际应用中得到了验证。
