Faculty of Pharmacy, University of Medicine and Pharmacy of Craiova, 200638 Craiova, Romania.
Faculty of Medicine, University of Medicine and Pharmacy of Craiova, 200638 Craiova, Romania.
Molecules. 2022 Dec 6;27(23):8604. doi: 10.3390/molecules27238604.
Palbociclib and abemaciclib are two cyclin-dependent kinases 4 and 6 used for breast cancer treatment. Levels of these medicines present a significant interindividual variability, so monitoring those concentrations might be necessary in therapy. Most of the methods presented so far in the literature use simple protein precipitation of plasma proteins as sample preparation method followed by direct injection of the supernatant into the LC instrument, preceded or not by a simple filtration step. Within that approach, the probability of injecting proteins in the chromatographic system is increased. With the purpose of obtaining a cleaner extract of the drugs, we developed and validated a simple and accurate LC-MS method for determining palbociclib and abemaciclib in human plasma. Solid phase extraction (SPE) using Oasis PRiME HLB cartridges was used for plasma sample preparation. The method provided clean extracts with a recovery extraction higher than 85% for both compounds. Separation was achieved by high-performance liquid chromatography (HPLC), using a C18 (4.6 × 50 mm) column, with a gradient elution of ammonium acetate/acetic acid-acetonitrile as the mobile phase. Detection was performed by mass spectrometry (MS) in single ion recording (SIR) mode. Intra-day and inter-day precision data for both analytes were 3.8-7.2% and 3.6-7.4%, respectively. Calibration curves were both linear between 2 and 400 ng/mL with a correlation coefficient higher than 0.998. The LC-MS method can be used to quantify the drugs in human plasma in routine analysis. The method proved to be useful in determining real plasma levels in patients involved in cancer therapy. Drug concentrations were determined in a 10 min run-time, including re-equilibration of the column.
帕博西尼和阿贝西利是两种用于乳腺癌治疗的细胞周期蛋白依赖性激酶 4 和 6。这些药物的水平存在显著的个体间变异性，因此在治疗中可能需要监测这些浓度。目前文献中提出的大多数方法都使用简单的血浆蛋白沉淀作为样品制备方法，随后直接将上清液注入 LC 仪器中，是否经过简单的过滤步骤。在这种方法中，将蛋白质注入色谱系统的概率增加。为了获得药物更清洁的提取物，我们开发并验证了一种简单、准确的 LC-MS 方法，用于测定人血浆中的帕博西尼和阿贝西利。固相萃取（SPE）使用 Oasis PRiME HLB 小柱进行血浆样品制备。该方法提供了清洁的提取物，两种化合物的提取回收率均高于 85%。分离通过高效液相色谱（HPLC）实现，使用 C18（4.6×50mm）柱，以乙酸铵/乙酸-乙腈作为流动相进行梯度洗脱。检测通过质谱（MS）在单离子记录（SIR）模式下进行。两种分析物的日内和日间精密度数据分别为 3.8-7.2%和 3.6-7.4%。校准曲线在 2 至 400ng/mL 之间均呈线性，相关系数均高于 0.998。LC-MS 方法可用于常规分析中定量测定人血浆中的药物。该方法在测定参与癌症治疗的患者的真实血浆水平方面证明是有用的。药物浓度在 10 分钟的运行时间内确定，包括色谱柱的重新平衡。
