Translational and Clinical Pharmacology
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2021
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IF 0
Hyeon-Cheol Jeong,Yo-Han Seo,Namyi Gu,Moo Yong Rhee,Kwang-Hee Shin
Candesartan and olmesartan are angiotensin II receptor blockers (ARBs) used for the treatment of hypertension and heart failure. Quantitation methods for candesartan and olmesartan were developed using ultra-high performance liquid chromatography-tandem mass spectrometry following protein precipitation. Candesartan was separated using 5 mM ammonium formate (A) and 100% acetonitrile (B) and olmesartan was separated using 2 mM ammonium formate with 0.1% formic acid (A) and 100% acetonitrile (B). Separation was performed using an isocratic method with a Thermo hypersil GOLD C18 column. Electrospray ionization was used for analyte ionization and detection of candesartan, olmesartan, and the internal standards by multiple reaction monitoring. Developed method showed excellent linearity ( r > 0.99) in the concentration range of 2–500 ng/mL for candesartan and 5–2,500 ng/mL for olmesartan. Accuracies were 86.70–108.8% for candesartan and 87.87–112.6% for olmesartan. These methods were able to successfully measure plasma candesartan or olmesartan concentrations in hypertensive patients. This study can be used for pharmacokinetic studies of candesartan or olmesartan in humans.
研究领域:
药理学
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分析化学
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DOI
PubMed
CURRENT PHARMACEUTICAL DESIGN
·
2024
·Vol. 30
·期 32
·2574-2585
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IF 2.6
Yuanjian Wang,Ruixun Wang,Huijia Wang,Ran Liu,Kaishun Bi,Qing Li
BackgroundEssential hypertension is a common clinical disease and a risk factor for cardiovascular and cerebrovascular diseases. Olmesartan medoxomil, amlodipine, and hydrochlorothiazide are commonly used antihypertensive drugs. The aim of this study was to establish a robust UPLC-MS/MS method for the simultaneous determination of olmesartan medoxomil, amlodipine, and hydrochlorothiazide in dog plasma. At the same time, the in vivo and in vitro release studies were conducted, and a preliminary in vitro-in vivo correlation (IVIVC) evaluation was performed.MethodsThe bioequivalence experiment was conducted with a double-crossed design. Three major components were extracted and analyzed by UHPLC-MS/MS. With the MRM scan, olmesartan and amlodipine were quantified by fragment conversion (m/z 447.10→190.10) and (m/z 408.95→294.00) under positive ESI mode, while hydrochlorothiazide was quantified with fragment conversion (m/z 295.90→268.90) under negative ESI mode. The in vitro release studies were performed using a USP paddle, and the dissolution medium was chosen from pH 6.0 to pH 6.8 according to the BCS classification of compounds. The IVIVC was calculated using the Wagner-Nelson equation.ResultsThe linear ranges of olmesartan, amlodipine, and hydrochlorothiazide in the plasma were 5.0-2500, 0.1-50, and 3.0-1500 ng/mL, respectively. All accuracies were within 3.8% of the target values, and the findings revealed that intra-day and inter-day accuracies were less than 12.1%. Moreover, the recoveries exceeded 88.3%, the matrix effect tests were positive, and the stability tests were positive. With the establishment of correlation, the distinguishable dissolution condition (pH 6.8) was selected as the predictable condition.ConclusionThe established method was suitable for the preclinical pharmacokinetic study of tripartite drugs with strong specificity and high sensitivity. Through the evaluation of IVIVC, the connection between in vivo and in vitro drug testing was initially established.
研究领域:
药理学
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分析化学
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临床医学
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DOI
PubMed
高影响因子
Drug Delivery and Translational Research
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2021
·Vol. 12
·期 3
·589-602
·
IF 4.617
Zhang Qihong,Feng Zongmiao,Ren Wei,Zhao Yunchun,Dushkin Alexandr V.,Su Weike
Hypertension is a common disease for human with high morbidity and mortality, and olmesartan medoxomil (OM) is widely used in the therapy of hypertension. However, poor water solubility and low bioavailability limit its widespread use. To improve the effect of OM, a ternary OM solid dispersion consisting of hydroxypropyl- β -cyclodextrin (HP- β- CD) and hydroxypropyl methylcellulose (HPMC) was prepared by mechanochemical method. The best preparation parameters were OM/HP- β -CD/HPMC-E5 with mass ratio of 1:2.6:1 and milling time of 4 h. Under the optimal preparation conditions, the solubility of the ternary solid dispersion could be increased by 12 times as compared with pure OM. Due to the addition of HPMC-E5, the solid dispersion had sustained release performance with prolonged release time of 12 h. Furthermore, in vivo study demonstrated that the prepared solid dispersion could afford significantly improved bioavailability of ~ 3-fold in comparison with pure drug. Hence, the prepared ternary solid dispersion of OM may be a promise delivery system for clinical application. Graphical abstract
研究领域:
药剂学
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高血压治疗
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药物递送系统
✓ 已验证
DOI
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
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2020
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IF 2.734
Qihong Zhang,Wei Ren,Alexandr V. Dushkin,Weike Su
Olmesartan medoxomil (OM) has been used in treatment of hypertension disease, as a prodrug of olmesartan. However, its clinical application is limited by the low oral bioavailability (~28%). Ternary solid dispersion of OM was prepared with hydroxypropyl- β -cyclodextrin and N -methyl- d -glucamine to improve its oral bioavailability using roll mill ML 007. Its physicochemical characterization was measured by scanning electron microscope, differential scanning calorimetry , powder X-ray diffraction and transform infrared spectroscopy . The solutions properties of OM in ternary solid dispersion were investigated involving the solubility, dissolution profiles, 1 H NMR analysis, phase solubility study and PAMPA study. Instrument analysis results revealed an amorphous solid dispersion had been synthesized without any side-products. It also showed enhanced solubility and dissolution rate in vitro . Pharmacokinetic study demonstrated an improved oral bioavailability in vivo . The rapid storage assay showed that the chemical stability of inclusion complexes had no change. The synthesized OM ternary solid dispersion is promising to be a better alternative to its pure formation in the market with improved oral bioavailability.
研究领域:
药剂学
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药物动力学
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药物传递系统
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产品关联
DOI
高影响因子
JOURNAL OF CHROMATOGRAPHY A
·
2020
·
IF 4.049
Qi Liang,Xiaoying Fu,Jianfeng Zhang,Jiaxue Hao,Gangjun Feng,Jing Wang,Qian Li,Faizan Ahmad,Xinfeng Zhao
The enormous growth in drug discovery paradigm has necessitated continuous exploration of new methods for drug-protein interaction analysis. To enhance the role of these methodologies in designing rational drugs, this work extended an immobilized angiotensin II type I receptor (AT 1 R) based affinity chromatography in antihypertensive compound identification. We fused haloalkane dehalogenase at C-terminus of AT 1 R and expressed the fusion receptor in E. coli. The expressed receptor was covalently immobilized onto 8.0 μm microspheres by mixing the cell lysate with 6-chlorocaproic acid-modified amino polystyrene microspheres. The immobilized AT 1 R was utilized for thermodynamic and kinetic interaction analysis between the receptor and four specific ligands. Following confirmation of these interactions by molecular docking, we identified puerarin and rosmarinic acid by determining their binding to the receptor. Azilsartan, candesartan, valsartan and olmesartan displayed two kinds of binding sites to AT 1 R by injection amount-dependent method. By molecular docking, we recognize the driving forces of the interaction as electrostatic interaction, hydrogen bonds and van der Waals force. The dissociation rate constants (k d ) of azilsartan, candesartan, valsartan and olmesartan to AT 1 R were 0.01138 ± 0.003, 0.05142 ± 0.003, 0.07547 ± 0.004 and 0.01310 ± 0.005 min −1 by peak profiling assay. Comparing with these parameters, puerarin and rosmarinic acid presented lower affinity (K A : 0.12 × 10 4 and 1.5 × 10 4 /M) and slower kinetics (k d : 0.6864 ± 0.03 and 0.3005 ± 0.01 min −1 ) to the receptor. These results, taking together, indicated that the immobilized AT 1 R has the capacity to probe antihypertensive compounds.
研究领域:
药理学
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药物发现
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生物化学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2024
·
IF 3.1
Yanan Guo,Shuang Cao,Bin Geng,Juanjuan Ma,Bo Yao
An online solid phase extraction–ultra performance liquid chromatography–tandem mass spectrometry detection method was developed for the simultaneous determination of sacubitril and seven sartan drugs in blood serum in this study. The compounds were separated through a C 18 column. Mass spectrometry of the samples was performed using a jet stream electrospray ion source (AJS, ESI+). The samples were detected via a multiple reaction monitoring (MRM) mode and quantified via a stable isotope internal standard method. 900 μL of prepared sample was injected and a run time of 12.5 minutes was obtained in this proposed method. The eight examined target compounds showed good linearity ( r 2 ＞0.994) in the corresponding mass concentration range and a lower limit of quantitation (LLOQ) was in the range of 0.05–0.1 μg/L. The recovery of the spiked serum samples ranged from 90.90 % to 106.20 % with relative standard deviations (RSDs) of 4.57 %–9.27 %. Five target compounds were detected in the actual serum samples using this method. The proposed method is simple to use, sensitive, accurate, and suitable for the trace detection of sacubitril and seven sartan drugs present in serum samples. The method can meet the needs for clinical monitoring of blood concentrations of this type of drug, while providing detection technology support for the development of compound preparations of sacubitril and other sartan drugs.
研究领域:
分析化学
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临床药理学
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药物分析
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF FOOD COMPOSITION AND ANALYSIS
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2023
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IF 4.3
Qinglin Wang,Hao Yuan,Xinyue Pan,Yiling Yang,Xiaosong Ma,Yahui Guo
The purpose of this study was to explore the feasibility and mechanism of synthesizing silver nanoclusters (AgNCs) using a double-stranded DNA (dsDNA) template and to use the AgNCs as probes for captopril detection. The results showed that the binding of silver ions towards DNA bases deduced the destruction of the initial dsDNA structure , and AgNCs with decent quantum yield (43.54%) were obtained. The detection using these AgNCs probes showed good performance for captopril , with a linear range of 0.1–0.8 μg·mL −1 and a detection limit of 0.045 μg·mL −1 . Recovery results in real samples of Apocynum venetum leaf tea and Ginkgo biloba leaf tablet demonstrated its good applicability. This work not only extended the understanding of DNA-AgNCs but also provided a fast and cost-effective tool for captopril detection.
✓ 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）