Quantification of letermovir in human serum using high-performance liquid chromatography with diode array detection

Development and Full Validation of a Bioanalytical Method for Quantifying Letermovir in Human Plasma Using Ultra-Performance Liquid Chromatography Coupled with Mass Spectrometry

“…The accuracy of all the QCs at different levels was within ±15%, and precision was ≤15%. Both the methods used in our study and in a previous study 14) conformed with the FDA guidelines for bioanalytical method validation, in terms of accuracy and precision. 15) Dilution linearity with human blank plasma was investigated at a ratio of 1 : 9.…”

“…3) Furthermore, according to a study conducted by Isberner et al, the median trough concentration of letermovir after oral administration of 240 or 480 mg in patients including children was 2603 ng/mL (range 175-12281 ng/mL), and two samples were less than 100 ng/mL. 14) These results suggest that letermovir In this study, a lower ULOQ than that used in a previous study (5000 ng/mL) 14) was chosen to improve the accuracy of our calibration curve, while a dilution integrity of 10-fold was assessed in order to account for concentrations above 1000 ng/mL.…”

“…The LLOQ determined in this assay (10 ng/mL) was lower than the LLOQ established in a previous study by Isberner et al (100 ng/mL). 14) Accuracy, Precision, and Dilution Linearity Table 2 summarizes the results of the intra-assay and interassay accuracy and precision. The accuracy of all the QCs at different levels was within ±15%, and precision was ≤15%.…”

“…11) In light of these findings, further studies for assessing the pharmacokinetics (PK) and pharmacodynamics (PD) are required. However, although multiple clinical studies 3,10,11,13) mention the use of LC/MS methods for quantifying letermovir in human plasma, there is no information regarding the full method, including its validation in the available literature. More recently, a new method for the quantification of letermovir in human serum using HPLC combined with diode array detector has been published.…”

“…More recently, a new method for the quantification of letermovir in human serum using HPLC combined with diode array detector has been published. 14) However, to date, no LC/MS method has been described in human plasma. Thus, the main purpose of this work was to develop and validate an ultraperformance liquid chromatography (UPLC)/MS method for quantifying letermovir in human plasma, which is suitable for clinical studies as well as for therapeutic drug monitoring.…”