Monitoring Concentration of Nirmatrelvir and Ritonavir by Ultra High Performance Liquid Chromatography-tandem Mass Spectormetry Method
10.3870/j.issn.1004-0781.2024.02.007
- VernacularTitle:超高效液相色谱-串联质谱法测定奈玛特韦及利托那韦血药浓度
- Author:
Jing FAN
1
,
2
;
Haoxiang TANG
;
Yinghui WANG
;
Weibin FAN
;
Jiao XIE
;
Bin LIN
Author Information
1. 浙江省长兴县人民医院药学部,长兴 313100
2. 湖州市智能药学与个体化治疗重点实验室,长兴 313100
- Keywords:
Nirmatrelvir;
Ritonavir;
Ultra high performance liquid chromatography-tandem mass spectormetry method(UPLC-MS/MS);
Coronavirus disease 2019(COVID-19)
- From:
Herald of Medicine
2024;43(2):190-195
- CountryChina
- Language:Chinese
-
Abstract:
Objective To establish a highly sensitive,stable,and universally applicable ultra-high-performance liquid mass spectrometry tandem method(UPLC-MS/MS)for simultaneous determination of nirmatrelvir and ritonavir blood concentrations in human plasma.Methods The separation was performed on an ACQUITY UPLC BEH C18 column(2.1 mm× 50 mm,1.7 μm)with gradient elution,and the mobile phase consisted of 0.1％formic acid-water and 100％acetonitrile at the flow rate of 0.3 mL·min-1.The column temperature was 45℃,and the injection volume was 2 μL.Electrospray ionization as ion source(ESI+)was used as the ion source and multiple reactions monitoring mode(nirmatrelvir m/z 500.20→319.10,nirmatrelvir-D9 m/z 508.59→328.10,ritonavir m/z 721.30→426.10,13C,2H3-ritonavir m/z 725.30→426.10)was adopted.Thirty patients with coronavirus disease 2019(COVID-19)treated with nirmatrelvir and ritonavir at the People's Hospital of Changxing County in Jan.2023 were selected to measure their steady-state trough concentrations of nirmatrelvir and ritonavir after 3 days of treatment.Results The linear range of nirmatrelvir was 0.100-10.0 μg·mL-1(R2=0.997 2),and the linear range of nirmatrelvir was 0.050-5.00 μg·mL-1(R2=0.995 2).The recovery rates of nirmatrelvir and lopinavir were both＞90％and the intra-batch and inter-batch precision relative standard deviations(RSDs)were both＜10％.Additionally,the recovery ranges for nirmatrelvir and lopinavir were 91.5％-97.0％,and the matrix effects ranged from 92.4％to 97.7％.The results of clinical samples showed that the plasma concentrations of nirmatrelvir and ritonavir in patients with COVID-19 varied greatly among individuals.Conclusion The method for simultaneous determination of nirmatrelvir and ritonavir concentrations in human plasma established in this study is convenient,highly specific,highly accurate,with high precision,which is suitable for monitoring the concentrations of nirmatrelvir and ritonavir in patients.
