A simple, rapid, cost-effective and sensitive high-performance liquid chromatography method with diode array detection was developed and validated for the quantification of letermovir, a compound approved for prophylaxis of cytomegalovirus infection and disease in adult recipients of an allogeneic hematopoietic stem cell transplant. Sorafenib was used as internal standard. Samples were pre-treated by liquid-liquid extraction with tert-butyl methylether. Separation was achieved on a XTerra® RP18 column (150 x 2.1 mm, 5 µm) at 30 °C using gradient elution with a mobile phase of 20 mM ammonium bicarbonate pH 7.9 (mobile phase A) and acetonitrile:20 mM ammonium bicarbonate (9:1 v/v) (mobile phase B). Samples were eluted at a flow rate of 0.3 mL/min throughout the 20-min run. UV wavelength mode was used, letermovir and sorafenib were monitored at 260 nm. The calibration curve was linear in a concentration range of 25 – 5,000 ng/mL with correlation coefficients ≥ 0.99. Intra-day and inter-day accuracy expressed as relative error were -11.4 – 20 % and -7.96 – 10.62 %, respectively. Precision expressed as coefficient of variation was 1.44 – 3.15 % (intra-day) and 1.17 – 1.93 % (inter-day). The method was successfully applied for analysis of 128 letermovir levels demonstrating its usefulness for letermovir monitoring in routine clinical practice.

开发了一种简单，快速，经济高效且灵敏的带有二极管阵列检测的高效液相色谱方法，并已用于定量letermovir，letermovir是一种批准用于预防同种异体造血干细胞移植的成年患者巨细胞病毒感染和疾病的化合物。索拉非尼用作内标。通过用叔丁基甲基醚进行液-液萃取对样品进行预处理。在XTerra®RP18色谱柱（150 x 2.1 mm，5 µm）上于30°C进行分离，使用20 mM碳酸氢铵pH 7.9的流动相（流动相A）和乙腈：20 mM碳酸氢铵（9）进行梯度洗脱：1 v / v）（流动相B）。在整个20分钟的运行过程中，样品以0.3 mL / min的流速洗脱。使用了紫外线波长模式，在260 nm处监测来特莫韦和索拉非尼。校正曲线在浓度范围为25 – 5,000 ng / mL时呈线性，相关系数≥0.99。以相对误差表示的日内和日间准确度分别为-11.4 – 20％和-7.96 – 10.62％。以变​​异系数表示的精度为1.44 – 3.15％（日内）和1.17 – 1.93％（日间）。该方法已成功地用于分析128个letermovir水平，证明了其在常规临床实践中对letermovir监测的有用性。15％（日内）和1.17 – 1.93％（日间）。该方法已成功地用于分析128个letermovir水平，证明了其在常规临床实践中对letermovir监测的有用性。15％（日内）和1.17 – 1.93％（日间）。该方法已成功地用于分析128个letermovir水平，证明了其在常规临床实践中对letermovir监测的有用性。