Iqbal Muzaffar, Wani Tanveer A, Khalil Nasr Y, Darwish Ibrahim A
Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P,O, Box 2457, 11451, Riyadh, Saudi Arabia.
Chem Cent J. 2013 Jan 14;7(1):7. doi: 10.1186/1752-153X-7-7.
Lenalidomide (LND) is a potent novel thalidomide analog which demonstrated remarkable clinical activity in treatment of multiple myeloma disease via a multiple-pathways mechanism. Validated sensitive method with high throughput is required for the determination of lenalidomide for pharmacokinetics and toxicokinetic studies. Ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) is a preeminent analytical tool for rapid biomedical analysis.
A simple, highly sensitive UPLC-MS/MS method was developed and validated for the determination of LND in rabbit and human plasma. After a simple protein precipitation using methanol, LND and carbamazepine (IS) were separated on Acquity UPLC BEH™ C18 column (50 × 2.1 mm, i.d. 1.7 μm, Waters, USA) using a mobile phase consisted of acetonitrile:water:formic acid (65:35:0.1%, v/v/v) pumped at a flow rate of 0.2 mL/min. LND and IS were eluted at 0.71 and 1.92 min, respectively. The mass spectrometric determination was carried out using an electrospray interface operated in the positive mode with multiple reaction monitoring (MRM) mode. The precursor to product ion transitions of m/z 260.1 > 149.0 and m/z 237.0 > 179.0 were used to quantify LND and IS, respectively. The method was linear in the concentration range of 0.23-1000 ng/mL with a limit of quantitation of 0.23 ng/mL. All the validation parameters were in the ranges acceptable by the guidelines of analytical method validation.
The proposed UPLC-MS/MS method is simple, rapid and highly sensitive, and hence it could be reliable for pharmacokinetic and toxicokinetic study in both animals and humans.
来那度胺（LND）是一种有效的新型沙利度胺类似物，通过多途径机制在多发性骨髓瘤疾病治疗中显示出显著的临床活性。在药代动力学和毒代动力学研究中，需要一种经过验证的高通量灵敏方法来测定来那度胺。超高效液相色谱 - 串联质谱法（UPLC - MS/MS）是用于快速生物医学分析的卓越分析工具。
开发并验证了一种简单、高灵敏的UPLC - MS/MS方法，用于测定兔和人血浆中的LND。使用甲醇进行简单的蛋白沉淀后，LND和卡马西平（内标）在Acquity UPLC BEH™ C18柱（50 × 2.1 mm，内径1.7 μm，美国沃特世公司）上分离，流动相为乙腈：水：甲酸（65:35:0.1%，v/v/v），流速为0.2 mL/min。LND和内标分别在0.71分钟和1.92分钟洗脱。质谱测定采用电喷雾接口，以正离子模式和多反应监测（MRM）模式进行。m/z 260.1 > 149.0和m/z 237.0 > 179.0的母离子到子离子的转变分别用于定量LND和内标。该方法在0.23 - 1000 ng/mL的浓度范围内呈线性，定量限为0.23 ng/mL。所有验证参数均在分析方法验证指南可接受的范围内。
所提出的UPLC - MS/MS方法简单、快速且高度灵敏，因此对于动物和人体的药代动力学和毒代动力学研究可能是可靠的。
