Analytical Methods
·
2018
·Vol. 10
·期 9
·1046-1053
·
IF 2.073
Lu Zhou,Liang Zou,Lili Sun,Hui Zhang,Wenkai Hui,Qiaogen Zou
Sacubitril–valsartan (SV) is a first-in-class inhibitor of the angiotensin II receptor and neprilysin for the treatment of chronic heart failure (HF) and hypertension. A stereoselective normal-phase high performance liquid chromatographic method was developed and validated for separation of sacubitril (SA), valsartan (VA) and their stereoisomeric impurities. Chromatography was performed using mobile phase A of n-hexane with 0.1% TFA added and mobile phase B comprising ethanol, isopropanol and TFA (80 : 20 : 0.1, v/v/v) and delivered at a flow rate of 1.0 mL min−1 on a Chiralcel OJ-H column (250 mm × 4.6 mm, 5 μm). The stereoisomers were monitored at a wavelength of 254 nm and the whole separation was achieved within 50 min. The method was validated in terms of specificity, linearity (R2 ≥ 0.998), accuracy (98.3–99.5%), precision (%RSD ≤ 1.82), limit of detection (0.06 μg mL−1 and 0.10 μg mL−1) and limit of quantification (0.2 μg mL−1 and 0.3 μg mL−1). The sample solution and mobile phase were found to be stable for at least 48 hours. The final optimized method was successfully applied to separate sacubitril–valsartan from their stereoisomers and showed characteristics of good repeatability and accuracy for quantitative determination of the stereoisomers in bulk drug.
研究领域:
药学
·
分析化学
✓ 已验证
产品关联
DOI
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
·
临床药理学
·
药物分析
✓ 已验证
产品关联
DOI
PubMed
高影响因子
KAOHSIUNG JOURNAL OF MEDICAL SCIENCES
·
2025
·
IF 3.1
Yan-Jun Yang,Jiu-Sheng Li
Sacubitril/valsartan (Sac/Val) has emerged as an effective compound with myocardium-protective functions in experimental and clinical trials for heart failure. This study investigated the function of Sac/Val in hypertensive heart disease (HHD) and explored the underlying mechanism. Spontaneous hypertensive rats (SHRs) were used as an animal model of HHD. Sac/Val administration ameliorated pathological injury, fibrosis, cell apoptosis, inflammatory cytokine production, and oxidative stress in the myocardial tissues of HHD rats. Similar findings were observed in vitro, where Sac/Val treatment reduced inflammation, oxidative stress, and fibrosis-related markers in Ang II-challenged H9C2 cells. Calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2) was identified as a target of Sac/Val which was downregulated in HHD models, and CAMKK2 protein levels were restored by Sac/Val treatment. Lentiviral vector-induced CAMKK2 knockdown reduced the phosphorylation levels of AMPKα, AKT, and GSK-3β, thereby negating the treatment effects of Sac/Val. Further treatment with AICAR, an AMPK agonist, significantly reactivated the AMPK/AKT/GSK-3β cascade and alleviated inflammatory injury in both models. Collectively, this study suggests that Sac/Val ameliorates inflammation and oxidative stress in HHD by restoring the CAMKK2 protein and activating the AMPK/AKT/GSK-3β cascade.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2023
·
IF 3.4
Quancheng Yang,Peng Cao,Yi Lv,Hua Peng,Xuejia Zhai
Pediatric heart failure (HF) is an important clinical disease with high hospitalization rates, morbidity, mortality and medical costs. Sacubitril/valsartan (also known as Entresto), was approved for the treatment of adult HF and is recently used in pediatrics. However, clinical therapy on children is more challenging than adults, and the pharmacokinetics of Entresto in children are still largely unknown and urgently needed. Herein, we aim to develop a simple and sensitive analytic method to monitor Entresto in pediatric patients, which is of great importance for individualized safe medication in children. Specifically, a liquid chromatography tandem mass spectrometry method for simultaneously quantification of valsartan, sacubitril and its bio-active metabolite sacubitrilat in human plasma has been developed and validated in pediatric patients. Plasma samples were pretreated with acetonitrile for protein precipitation. Elution was performed on X Select HSS T3 column (2.1 × 100 mm, 5 µm; Waters) column using an isocratic mobile phase process consisting of 0.1% formic acid aqueous solution and 0.1% formic acid acetonit rile with a total run time of 3.0 min. Valsartan-d3, sacubitrilin-d4 and sacubitrilat-d4 were used as the corresponding deuterium internal standards. According to the Bioanalytical Method Validation Guidance for Industry, the method was validated in the range of 0.5–5000 ng/mL. Intra- and inter-day accuracy of sacubitril,valsartan and sacubitrilat ranged from 93%− 108%, 98%− 109%, 91%− 102%, respectively, with relative standard deviation of precision ranging from 2.0% to 5.1%, 2.4%− 7.5%, 1,3%− 7.4%. The proposed method demonstrated good accuracy, precision and linearity. The matrix factors normalized by internal standard meet the acceptance criteria. The method was fully validated and applied in 39 children. Trough concentration of the three substances to be measured were: valsartan (11.3–938.0 ng/mL), sacubitril (0.5–395.5 ng/mL) and sacubitrilat (522.1–4890.0 ng/mL). Overall, this is the first study to simultaneously determined the plasma valsartan, sacubitril and sacubitrilat concentrations in children, which is believed to facilitate the clinical management of pediatric HF.
研究领域:
药理学
·
儿科学
·
临床医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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