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.
研究领域:
药理学
·
分析化学
·
临床医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Omega
·
2024
·
IF 3.7
Dongchen Zhou,Jiahui Wu,Qingcheng Wang,Yong Liu,Shiqi Wang,Weizong Zhang,Yunfeng Zhang,Huizhi Ding,Yunfei Shao,Haixing Wang,Qing Shen
Precise administration of tirofiban must be carefully considered to achieve the best treatment efficacy and maximize safety for patients. Herein, a paper spray ionization (PSI) linear ion trap (LIT) portable mass spectrometer (pMS) based point-of-care testing (POCT) technique was developed for on-site sampling, clinical testing, and immediate analysis of tirofiban blood drug concentrations. The results showed that tirofiban formed a significant and stable parent ion peak at m/z 441.3 by MS1 full scan in positive ion mode, which fragmented into product ions at m/z 395.4, m/z 321.3, m/z 276.3, and m/z 260.3 through collision-induced dissociation (CID) in MS/MS. To improve ion response, the parameters were optimized to the voltages of ionization 3600 V, ion isolation 1 (ISO1) 8 V, ion isolation 2 (ISO2) 2 V, and collision-induced dissociation (CID) 3 V. This method was validated, and the limit of detection (LOD) and limit of quantification (LOQ) were found to be 10.1 and 33.7 μg·L–1, respectively. For precision, it had the relative standard deviation (RSD) of interday precision of 4.8 to 6.7% and the RSD of intraday precision of 7.8 to 8.3%. The recovery of the method ranged from 87.5 to 93.4%. Although matrix effects in blood samples had some inhibitory effects on the target signal formation, the method compensated for part of the matrix effects by establishing a matrix-matched calibration curve, which exhibited good linearity with a R2 of 0.9987. Finally, the method was applied to the detection of tirofiban in clinically collected blood samples. Out of 12 samples, ten had tirofiban concentrations between 35.4 and 72.1 μg·L–1 while the remaining two were below the LOQ. The method needs further optimization and validation in the future to improve its sensitivity and stability.
研究领域:
分析化学
·
临床医学
·
心血管病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2018
·
IF 3.457
Miao Yan,Zhu-feng Wu,Dan Tang,Feng Wang,Yi-wen Xiao,Ping Xu,Bi-kui Zhang,Yi-ping Liu,Da-xiong Xiang,Hoan Linh Banh
Voriconazole (VRC) and proton pump inhibitors (PPIs) have similar metabolic pathways. The objectives of the study are to evaluate the impact of PPIs on the pharmacokinetics of VRC. Human liver microsomes model was applied to assess the inhibitory effects of PPIs on the metabolism of VRC in vitro. A retrospective study was also carried out to explore the relationship between the plasma VRC trough concentrations and PPIs uses. Patients were divided into six groups: control (n = 166), lansoprazole (LAN, n = 38), esomeprazole (ESO, n = 19), omeprazole (OME, n = 45), pantoprazole (PAN, n = 43), and ilaprazole (ILA, n = 38) groups. All five PPIs showed concentration-dependent inhibitory effects on the VRC metabolism in human liver microsomes, among which LAN, OME and ESO were three of the most potent inhibitors. Consistently, co-administered with LAN, OME and ESO significantly increased the plasma VRC trough levels ( p < 0.05), whereas there was no significant association between VRC concentrations and PAN or ILA use. Interestingly, patients in the PPIs groups were more likely to reach the therapeutic VRC range of 1–5.5 μg/mL in steady state when compared with control patients (75–81% VS 69%). In conclusion, although all PPIs showed inhibitory effects on the VRC metabolism in vitro, only LAN, OME and ESO significantly increased VRC plasma concentrations. This study should be helpful for choice of the type of PPIs for patients administered with VRC.
研究领域:
临床药理学
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药物代谢
·
医学研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
AAPS PHARMSCITECH
·
2020
·Vol. 21
·期 8
·1-11
·
IF 2.401
Su Yanping,Lu Wenxiang,Fu Xiaoling,Xu Ying,Ye Lixiang,Yang Jian,Huang Huihui,Yu Changxi
The aim of this study was to develop a suitable drug-in-adhesive patch for transdermal delivery of koumine. Acrylic polymer Duro-Tak® 87-4287, which contains hydroxyl groups, may significantly enhance the skin permeation of koumine from transdermal patches containing 0.93–3.72% koumine. Among permeation enhancers, 10% azone showed the greatest potential and increased the flux of koumine to 1.48-fold that of the control. Therefore, an optimized patch formulation containing 3.72% koumine and 10% azone in Duro-Tak® 87-4287 that offers good physical properties was selected for an in vivo pharmacokinetic study using rats. The maximal plasma drug concentration ( C max ) of koumine after transdermal administration (4 mg/patch) was 25.80 ± 1.51 ng/mL, which was in the range of those after oral administration (3 mg/kg and 15 mg/kg). The time to the maximal concentration ( T max ) and the half-life ( t 1/2 ) of the drug with transdermal administration were 3.96 ± 0.46 h and 21.10 ± 1.36 h, respectively, which were longer than those with oral administration. Furthermore, the area under the concentration-time curve (AUC 0–72 h ) of 898.20 ± 45.57 ng·h/mL for the transdermal patch was much higher than that for oral administration (15 mg/kg). In conclusion, the drug-in-adhesive patch containing koumine provides a steady plasma koumine level and sustained release in vivo and can be an effective means of transdermal delivery for koumine.
研究领域:
药学
·
药理学
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
REGULATORY TOXICOLOGY AND PHARMACOLOGY
·
2025
·
IF 3.5
Liqiang Gu,Yanping Hu,Yinfang Lai,Sheng Zhang,Haoran Wang,Xiaozhen Xu,Lingfang Chen,Yuhua Shi,Jiechao Chen,Xiaochun Sun,Yuan Zhang,Lingzhi Hu
Bioequivalence test is typically conducted by determining the drug concentration in plasma. However, this is not suitable for brain drugs (like Edaravone) that have targets in CNS. The amount of a drug in target site in the CNS is responsible for its activity in the brain, while the concentration of a drug in the blood has a weak impact on the CNS. In this paper, a new consistency evaluation method for brain drugs was established. 16 rats were divided into two groups. One group was administered the test preparation, and the other group was administered the control preparation. Then, cerebrospinal fluid (CSF) samples were collected. All of the CSF samples were examined by LC-MS. The 90 % confidence interval of the geometric mean ratio of AUC 0-t was 90.30–150.59 %, and 91.79–211.06 % for C max . In addition, the result indicated that the two preparations were not bioequivalent in the CNS, although the concentration-time profile and pharmacokinetic parameters were quite similar. The results revealed the particularity and complexity of the bioequivalence test for brain drugs that have targets in the CNS. The feasibility of the test was confirmed, and our results provide useful information for the consistency evaluation of brain drugs.
研究领域:
药理学
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神经科学
·
药物研究
·
分析化学
·
药物开发
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2022
·
IF 16.744
Bo Zhu,Jie Shi,Huanchao Sun,Lixin Xia,Weisen Fang,Hongjian Li,Wanshun Liu,Baoqin Han
Chitosan and its water-soluble derivatives have been widely used in biomaterials, but their disadvantages have hindered their widespread application. In this study, butyryl chitosan, a liposoluble chitosan derivative, was prepared by introducing butyryl groups into chitosan molecules through an acylation reaction. The synthesis conditions were optimised, the reaction was more efficient and simpler than previously reported strategies. Two butyryl chitosan with degrees of substitution greater than two were synthesised. Chemical characterisations confirmed that the hydroxyl and primary amine groups in the backbone of chitosan were converted into amide and ester groups, respectively. The butyryl chitosan films have advantages such as high mechanical properties, long biodegradation time, proper surface charge, good cytocompatibility, and histocompatibility. Butyryl chitosan was used as carrier to prepare an implantable tacrolimus sustained release film. Characterization results showed that tacrolimus existed in an amorphous state in the release film. This work embodies an innovative formulation using tacrolimus-loaded carboxymethyl chitosan amorphous solid dispersions embedded butyryl chitosan film with added advantage of sustained release, an effective blood concentration in vivo for 11 days and a systemic exposure but lower intrapatient variability in tacrolimus trough levels. This work merits sustainable tacrolimus release use by providing application-based proofs and qualifies as a potential formulation for sustainable tacrolimus release system. We expect an improvement in terms of therapeutic compliance with positive effects on allograft outcomes.
研究领域:
生物材料
·
药学
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药物递送系统
·
聚合物化学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2023
·
IF 5
Xin Liu,Wei Niu,Jiamin Liu,Zhao Cui,Jiazheng Li,Zhenhai Zhang,Jianming Ju
β-cyclodextrin and hydroxypropyl-β-cyclodextrin were combined with baicalein to improve its solubility in water. The physicochemical properties and pharmacokinetic characteristics of the two complexes and their therapeutic effects on dextran sulfate sodium-induced ulcerative colitis were studied in mice. Differential scanning calorimetry , X-ray diffraction, infrared spectroscopy , and scanning electron microscopy showed that the two complexes were successfully prepared and significantly improved baicalein's solubility and dissolution. The t 1/2 , C max , and AUC 0-∞ values of the inclusion complexes were substantially better than those of the original drug in rats. Analysis of the tissue distribution of acute ulcerative colitis in mice showed that the peak concentrations of baicalein and its metabolite, baicalin , in the small intestines, liver, and colon were higher than that of the free drug. The therapeutic effect of the inclusion compound was significantly better than that of the original drug. This study provides a new reference for applying cyclodextrin inclusion complex in ulcerative colitis.
研究领域:
药剂学
·
药理学
·
胃肠病学
·
药物递送系统
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2020
·
IF 2.734
Rui Bao,Qi-Long Wang,Ran Li,Michael Adu-Frimpong,Elmurat Toreniyazov,Hao Ji,Xi-Ming Xu,Jiang-Nan Yu
6-Shogaol is one component of ginger, which has been described to possess various health-promoting effects including anticancer, antiinflammatory, antioxidant and antiatherogenic. However, poor water solubility has limited the aforementioned health benefits and clinical applications of the drug. Herein, the aforementioned drawback was circumvented by the preparation of 6-shogaol-loaded liposome through thin-film dispersion method with TPGS as the carrier, in comparison with 6-shogaol liposome and free 6-shogaol. Appropriate indices were used for the characterization of the developed liposomes viz., particle size (PS), zeta potential (Z-potential), polydispersity index (PDI), entrapment efficiency (EE) and loading capacity (LC) while their morphologies were observed under the transmission electron microscopy (TEM). In-vitro dissolution investigation showed a substantial improvement in the accumulative release rates of liposomes comparable to the free 6-shogaol. The TPGS-modified 6-shogaol and 6-shogaol liposomes had oral relative bioavailability (RBA) of 580.04% and 281.55%, respectively, with improved t 1/2 , MRT, C max , AUC 0-t and T max . Pertinently, the TPGS coated 6-shogaol liposome may enhance the targeting of the drug to the brain. Therefore, the TPGS coated 6-shogaol liposome could potentially improve oral bioavailability of lipophilic drug in-vivo . More importantly, the results of tissue distribution investigation suggest that TPGS coated 6-shogaol liposome may act as promising carrier for brain delivery in future.
研究领域:
药剂学
·
药理学
·
纳米技术
·
药物递送系统
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）