JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2023
·
IF 3.4
Fenglun Zhao,Zheng Xiang,Junping Han,Jie Pan,Yuchen Qu,Kai Fan,Zhiqiang Wu,Delai Xu,Yunli Yu,Zhu Shen,Cunjin Su
In December 2021, the U.S. Food and Drug Administration (FDA) granted emergency authorization for Paxlovid® as an antiviral treatment for COVID-19. Paxlovid® is composed of two tablets, nirmatrelvir and ritonavir. Dose adjustment is necessary in cases of renal insufficiency. The aim of present study is to establish a LC–HRMS method for simultaneous determination of nirmatrelvir/ritonavir in human serum for therapeutic drug monitoring. Internal standard saquinavir was added in 25 μL human serum samples, and then the samples were precipitated with methanol. The analytes were separated by gradient elution on a C18 column, using a mobile phase of 0.1 % formic acid-water and methanol, at a flow rate of 0.4 mL/min. The injection volume was 2 μL, and the analysis time was 5 min. The determination of the analytes was performed by electrospray ionization in positive mode by full mass monitoring. The detected ions of nirmatrelvir, ritonavir and saquinavir were m/z 500.24792, 721.32004 and 671.39155, respectively. The linear concentration range for nirmatrelvir was 78.13–20000 ng mL −1 , for ritonavir was 15.63–4000 ng mL −1 (r 2 ＞0.9900). The accuracy ranged from 87.45 %∼104.63 %, and the intra-day and inter-day precision RSD was <15 %. The recovery of nirmatrelvir ranged from 98.72 %∼109.83 %, and that of ritonavir was 95.41∼112.36 %. The matrix effect of nirmatrelvir was 88.31∼97.73 %, and that of ritonavir was 85.17∼103.05 %. This method was used to measure the trough concentrations of nirmatrelvir/ritonavir in 17 patients. The trough concentration of nirmatrelvir was 1331.7–8352.5 ng/mL, and that of ritonavir was 53.4–1325.5 ng mL −1 , with large individual differences. The method is simple, sensitive, specific, and reproducible, and can be used for monitoring the blood concentration and pharmacokinetic study of nirmatrelvir/ritonavir in COVID-19 patients.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
·
2024
·
IF 2.8
Zong-liang Xu,Cheng-jian Li,Xian Qian,Hu Duan,Jin Zhou,Qian-qian Zhang,Xin Dong,Liang Zhao
Antiviral treatment for COVID-19 is considered an effective tool in reducing the rate of severe cases and deaths. As of June 2023, a total of six small molecule antiviral drugs have been conditionally approved for marketing by the National Medical Products Administration (NMPA) within China. In this study, a method of HPLC-MS/MS was established and validated for the determination of six small molecule antiviral drugs in plasma using Lamivudine as an internal standard. The chromatographic separation was performed using gradient elution with an ACE 3 C 18 -PFP column (3.0 mm × 150 mm, 3 μm), and the mobile phase consisted of deionized water and acetonitrile/water (90:10, v/v), both with 10 mmol/L of ammonium acetate and 0.1 % ammonium hydroxide added. Quantitative analysis of the six small molecule drugs was carried out through selective reaction monitoring based on the positive ion spray ionization mode. The method exhibited excellent precision, accuracy, recovery, and linearity, and it was used to determine the pharmacokinetic characteristics in rats. Our work not only established a bioanalytical method for six small molecule antiviral drugs but also provided scientific references for clinical pharmacokinetic studies.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
THERAPEUTIC DRUG MONITORING
·
2025
·
IF 2.4
Ma Zhiyuan,Bai Mengru,Shen Shuying,Zhou Junshan,Dong Rong,Zhang Jiangjun,Weng Yayun,Li Li,Li Yongchen,Liu Dan,Yan Wei,Lin Nengming,Xia Jianmei
Background: Nirmatrelvir/ritonavir is licensed for the treatment of mild-to-moderate coronavirus disease (COVID-19) in patients at an increased risk of progression to severe disease. However, data on the real-world plasma exposure to nirmatrelvir/ritonavir remain limited, particularly in Chinese patients. This study aimed to assess the nirmatrelvir/ritonavir trough concentration (C trough ) and identify its critical factors in hospitalized Chinese patients treated with nirmatrelvir/ritonavir 300 mg/100 mg twice daily over a 5-day course. Methods: A high-performance liquid chromatography-tandem mass spectrometry assay was developed and validated to measure the nirmatrelvir/ritonavir C trough . Correlation analyses were performed to identify the variables influencing nirmatrelvir/ritonavir C trough . Results: Among the 110 patients, 100% had plasma concentrations above the antiviral in vitro 90% effective concentration. The median C trough of nirmatrelvir was 4.55 mcg/mL (15.6× 90% effective concentration), ranging from 0.65 to 12.44 mcg/mL. Nirmatrelvir C trough in normal and mild renal impairment cohorts were comparable (4.09 ± 1.97 mcg/mL and 4.57 ± 2.21 mcg/mL) but significantly increased in the moderate renal impairment cohort (6.41 ± 2.31 mcg/mL). Sex, age, and obesity were not significantly associated with nirmatrelvir exposure. Conclusions: Nirmatrelvir C trough was high in Chinese patients with COVID-19, and therapeutic drug monitoring should not be routinely recommended, except in patients with renal impairment.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）