JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
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2020
·
IF 3.004
Chen Sun,Mingyu Zhang,Yanhong Zhao,Jianxin Pang,Ying Peng,Jiang Zheng
Urate anion exchanger 1 (URAT1) expressed in the proximal renal tubules is responsible for about 90% of the reabsorption of uric acid. URAT1 is identified as an important target of uricosuric drugs. Here we present an LC-MS/MS-based approach, combined with URAT1-transgenic MDCK cells, for the assessment of uric acid. Cell lysis was executed with 50 mM NaOH to release uric acid. 1,3- 15 N 2 uric acid was employed as the internal standard. The harvested uric acid, along with the stable isotope-labeled uric acid, was analyzed by LC-MS/MS in multiple reactions monitoring and negative modes. Validation, i.e. determination of selectivity, precision, accuracy, extraction recovery, and matrix effect, and feasibility was evaluated by use of the approach developed. The linearity was observed in the range of 1.0–250 μM (r = 0.9960) with limit of detection of 50 nM and limit of quantitation of 200 nM. The precision and accuracy were found to be RSD ≤ 20% and 80–120% of the nominal value, respectively. Uric acid uptake showed concentration and time dependency in URAT1-transgenic cells. The observed inhibitory effects of three URAT1-targeted uricosuric drugs were consistent with those reported in literature. The stable isotope dilution-based approach was proven to be selective, sensitive, and convenient, which is a good in vitro model for URAT1-targeted drug candidate screening.
研究领域:
药理学
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分析化学
·
医学
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产品关联
DOI
PubMed
高影响因子
Bioanalysis
·
2025
·
IF 1.8
Kaiwei Luo,Danrui Liu,Shengshuo Zhang,Xin Zhang,Qunan Cheng,Jie Lin,Yonghua Yu
Aims This study aimed to establish a robust LC-MS/MS method for quantifying trazodone in human plasma and investigate its pharmacokinetic profile in healthy Chinese subjects under fasting and fed conditions.Materials & methods A validated LC-MS/MS method using protein precipitation was applied to analyze trazodone in 68 healthy subjects (34 fasting/34 fed), with full method validation performed.Results This method exhibited high selectivity, precision, and accuracy. The results showed good linearity in the range of 5–3000 ng/mL and matrix effect results showed no matrix interference. The pharmacokinetic data revealed notable differences between the fasting and postprandial states.Conclusions The validated LC-MS/MS method proved reliable for trazodone quantification. The observed food effects on absorption suggest clinical dosing should consider administration conditions to ensure optimal therapeutic outcomes.
研究领域:
分析化学
·
药理学
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临床医学
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产品关联
DOI
PubMed
高影响因子
COMBINATORIAL CHEMISTRY & HIGH THROUGHPUT SCREENING
·
2024
·
IF 1.6
Yuanxia Yang,Miaoting Yang,Lijuan Wang,Liufang He,Tao Shi
Background: The establishment and validation of methods for testing biological samples are crucial steps in pharmacokinetic studies. Currently, several methodological reports have been published on the detection of rapamycin plasma concentrations. Objective: The objective of this study was to explore an effective method for detecting rapamycin in rat whole blood biological samples. Method: In this study, we designed a rapid, sensitive, and specific liquid chromatograph-mass spectrometer/mass spectrometer (LC-MS/MS) methodology for detecting rapamycin in rat whole blood biological samples. We comprehensively validated the specificity, linear range, lower limit of quantification (LLOQ), precision, accuracy, recovery, and stability of this method. Results: The findings of this study confirmed the successful implementation of LC-MS/MS for the detection of rapamycin, demonstrating its sensitivity, specificity, and reliability in quantitative analysis. This method ensures the accuracy and reliability of subsequent study data through our validated LC-MS/MS approach. Conclusion: The results demonstrated the successful implementation of an LC-MS/MS method for sensitive, specific, and reliable quantitative analysis of rapamycin in rat whole blood samples. This method ensures the accuracy and reliability of subsequent study data. Significance: The importance of this study lies in the successful establishment of a rapid, sensitive, and specific LC-MS/MS method for detecting rapamycin concentration in rat whole blood, ensuring the accuracy and reliability of subsequent research data. This provides a crucial tool and foundation for further understanding the metabolism and pharmacological effects of rapamycin in vivo, aiding in the advancement of drug research and clinical applications in related fields.
研究领域:
药代动力学
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药物分析
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生物样本检测
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DOI
PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
·
2022
·
IF 3.318
Xuan Guo,Lei Zhang,Zihan Lei,Zhe Hou,Hui Li,Xiaodong Li,Jing Dong,Ling Song,Dingding Chen,Dongyang Liu
Objective The aim of this study is to develop a LC-MS/MS method for the quantitation of seven cytochrome P450 (CYP450) enzymes. Methods A high-performance liquid chromatography-tandem mass spectrometry method was developed using multiple reaction monitoring mode with positive electrospray ionization. The method was validated with selectivity, linearity, stability, accuracy and precious. In addition, the abundance of seven CYP450 enzymes in human liver microsomes and CYP3A4 in placenta were determined using the current method. Results The linear range for CYP1A2, CYP2B6 and CYP2C8 was 0.036–3.6 nM and for CYP2C9, CYP2C19, CYP2D6 and CYP3A4 was 0.090–9.0 nM. No interference was found between the blank matrix and each specific peptides. The accuracy and precious results were in accord with the requirement of analytical methods for biological samples in Chinese Pharmacopoeia. In addition, the peptides were stable under current stability conditions. The content of CYP3A4 in placenta and the seven CYP450 enzymes in human liver microsomes were accurately quantified. Conclusion The developed method is sensitive and specific and can be applied to the quantification of enzymes abundance in different human derived samples like placenta and liver microsomes.
研究领域:
药理学
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分析化学
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生物化学
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产品关联
DOI
PubMed
高影响因子
ARCHIVES OF PHARMACAL RESEARCH
·
2016
·Vol. 39
·期 12
·1653-1662
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IF 2.49
Kim Han Sol,Cho Ha Ra,Ho Myoung Jin,Kang Myung Joo,Choi Yong Seok
Osteoarthritis (OA) is the most common type of arthritis. To manage OA, in general, oral administration of non-steroidal anti-inflammatory drugs (NSAIDs) is used. Recently, the analgesic and anti-inflammatory efficacy of piroxicam (PX), a long-acting NSAID, by intra-articular (IA) administration in OA was reported, and the possibility that PX is distributed in articular tissues at a certain concentration was raised. Thus, herein, novel LC–MS/MS methods to detect PX in rat articular tissue and plasma are presented. For articular tissue, solvent extraction with acetonitrile for 12 h was employed and a protein precipitation method was used for the preparation of a plasma sample. The developed methods were validated by following the FDA guidelines, and the validated methods were successfully applied to a PK study of IA PX. The present study presents, to our knowledge, the first method of determining a drug in articular tissue. Additionally, the level of PX in articular tissue after IA PX administration was experimentally confirmed for the first time using the present methods. Therefore, the present methods provide a new direction for in vivo evaluation for IA PX formulations and contribute to the development of alternative IA PX formulations with better effects for the treatment of OA.
研究领域:
药理学
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分析化学
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骨科
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产品关联
DOI
PubMed
高影响因子
Current Pharmaceutical Analysis
·
2021
·Vol. 17
·期 10
·1249-1256
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IF 0.89
Sun Qian,Yang Yu-fei,Zou Qiao-gen,Xia Yun-yan,Han Cheng-qun
Background: A liquid chromatography-tandem mass spectrometric (LC-MS/MS) method had been developed for the quantification of acotiamide in rat plasma and been applied to pharmacokinetic studies. However, there was no LC-MS/MS method been developed for the determination of acotiamide
in human plasma and its pharmacokinetic study. Objective: A simple and fast LC-MS/MS method was established and validated for the quantification of acotiamide in human Received: plasma and was applied to a pharmacokinetic study. Methods: Sample preparation was accomplished Revised:
Accepted: through protein precipitation, and chromatographic separation was achieved on a Welch, Ultimate XB-C18 column (2.1×50 mm, 3 μm) with a security guard cartridge C18 using a binary gradient with DOI: mobile phase A (Methanol) and B (the solution of 10 mM Ammonium acetate with
0.1% Formic acid) at a flow rate of 400 μL/min. Results: The retention time of acotiamide and its internal standard, acotiamide-d6 was 1.78 min and 1.79 min, respectively. The total run time was 4.0 min. The method was developed and validated over the concentration range of 0.500-100
ng/mL for acotiamide, with correlation coefficient greater than 0.9987. The extraction recovery was more than 108.43% and the matrix effect was not significant. The inter- and intra-day precisions were below 5.80% and accuracies ranged from 92.7 to 103.0%. Acotiamide was demonstrated to be
stable in human plasma under the tested conditions. Conclusion: The validated LC-MS/MS method was successfully applied to study the pharmacokinetic profiles of acotiamide in human plasma after oral administration and has achieved satisfactory results.
研究领域:
药物分析
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临床药理学
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DOI
高影响因子
Analytical Methods
·
2024
·Vol. 16
·期 16
·2472-2477
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IF 2.7
Chenhao Zhao,Xingdan Wang,Jing Wu,Yeli Hu,Qiwei Zhang,Qi Zheng
Sialic acids are a family of monosaccharides that share a nine-carbon backbone and a carboxyl group. A recent derivatization method based on 3-nitrophenylhydrazine (3-NPH) provides a mild chemical labeling technique for biomolecules containing carbonyl or carboxyl groups. In this study, we utilized 3-NPH to label sialic acids via a two-step derivatization process. The derivatized species can produce a common reporter ion corresponding to C1–C3 with two labels, and a fragment differentiating between Neu5Ac, Neu5Gc, and KDN. This method is compatible with O-acetylated sialic acids and provides high sensitivity to Neu5Gc and KDN, and since the utilization of dual labeling significantly enhances the hydrophobicity of derivatives, it can effectively mitigate matrix effects when combined with parallel reaction monitoring technology. Negative-ion tandem mass spectrometry (MS/MS) analysis reveals a distinctive fragmentation profile for the 4-O-acetylated species, while the other sialic acids yield similar MS/MS spectra with a high abundance of reporter ions. Using the reporter ion as a transition, this analytical strategy is effective for analyzing complex biological samples. For example, it was successfully employed to quantify sialic acids in the intestinal tissues of several carp species, demonstrating its potential in sialylation research.
研究领域:
分析化学
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糖生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF SEPARATION SCIENCE
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2022
·Vol. 45
·期 14
·2543-2554
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IF 3.614
Lu-Ning Sun,Yang Zhao,Hua-Ye Gao,Yan-Ling Yang,Xu-Ping Qian,Shi-Yu Sun,Yu Wang,Li Ding,Yong-Qing Wang
Pivmecillinam, the ester of biologically active antibiotic mecillinam, is an effective oral preparation to treat urinary tract infections. To study pharmacokinetics in humans, LC-MS/MS methods were developed to quantify pivmecillinam and mecillinam in human plasma, respectively. Considering cephalexin as internal standard, analytes were separated on UltimateXB-C18 columns after protein precipitation by acetonitrile. The mobile phase was composed of water containing 0.1% formic acid and methanol. The multiple reactions monitoring transitions of m / z 440.2→167.1, 326.1→167.1, and 348.1→158.1 were selected to inspect pivmecillinam, mecillinam, and the internal standard in positive ion mode. No apparent matrix effect was perceived. Linearities were obtained over calibration ranges of 0.0500–12.0 and 10.0–15,000 ng/mL, respectively. The intraday precisions were below 5.5%, the interday precisions were below 6.1%, and accuracies were within –8.1 to 13.0%. Stability tests were conducted and an acidification step was explored to enhance the stability of pivmecillinam and mecillinam. Further stability was validated under various storage and processing conditions. Both methods were applied to a pharmacokinetic study of pivmecillinam and mecillinam after oral administration of 400 mg pivmecillinam hydrochloride tablets in healthy Chinese subjects.
研究领域:
分析化学
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药理学
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临床医学
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产品关联
DOI
PubMed
高影响因子
Toxins
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2024
·Vol. 17
·期 1
·11
·
IF 3.9
Hui-Qin Pan,Rui Feng,Yan-Nan Tan,Xiao-Ya Qin,Yi-Min Cao,Xiu-Hong Mao,Qing Hu,Heng Zhou
Puberulic acid (PA) is a mycotoxin produced by a species ofPenicillium. It has received widespread attention as a significant contributor to the reported fatalities associated with red yeast rice dietary supplements. However, the detection of PA, especially at low concentration levels, poses a considerable challenge, with no detection methods reported thus far. Here, we present a simple and sensitive derivatization-based LC-MS/MS method, requiring no purification processes, for determination of PA in the red yeast rice. The methylating derivatization with trimethylsilyldiazomethane (TMSCHN2) was performed to enhance its analytical performance. To achieve optimal detection sensitivity, the amount of solvent and TMSCHN2for the derivatization reaction, along with the reaction time, were individually optimized. Moreover, sample extraction solvent was carefully chosen to improve recoveries in real sample analyses. Comparatively, the proposed LC-MS/MS method achieved a superior detection sensitivity, over 100-fold higher than that of the liquid chromatography method. A good linear relationship within the concentration range of 5 ng/mL to 200 ng/mL (with a linear correlation coefficient of 0.99952) was demonstrated by the method validation. The average recovery rate was between 82.2% and 84.2%, and the repeatability (RSD of 2.1% to 10.4%, n = 6) was satisfactory. The derivatized PA remained stable within 48 h. The limit of detection and the limit of quantification could reach 2 μg/kg and 50 μg/kg, respectively. As a result, the method was successfully applied to detect PA in over 42 batches of the red yeast rice samples. It indicated a low risk of PA contaminations in the red yeast rice products made in China. Furthermore, its application to the other health food products containing red yeast rice demonstrated the applicability of the established method.
研究领域:
食品科学
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分析化学
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毒理学
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产品关联
DOI
PubMed
高影响因子
Bioanalysis
·
2024
·
IF 1.9
Xiemin Qi,Ning Chen,Qinxin Song,Yanan Chu,Haiping Wu,Jingwen Shan,Huijie Yue,Guohua Zhou
Aim: Differences are existed in the bioactivity among various vitamin K (VK) forms. To investigate the correlation between clinical parameters of initial anticoagulation and plasma levels of VK1 and VK2 (MK-4 and MK-7), it was necessary to establish a quantitative method for simultaneous determination.Materials & methods: Plasma samples in cardiovascular patients were extracted by cyclohexane and analyzed using a C18 column. Baseline concentrations of VK1, MK-4 and MK-7 were 0.98 ± 0.52 ng/ml, 0.45 ± 0.13 ng/ml and 0.65 ± 0.31 ng/ml, respectively. The concentrations of MK-7 and total VKs were significantly relevant to INR0, respectively (p = 0.010 and p = 0.048, respectively).Conclusion: Thus, when adjusting anticoagulation dosage, concentrations of various VK homologues might be considered.
研究领域:
医学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYTICA CHIMICA ACTA
·
2023
·
IF 6.2
Shaoran Tang,Pei Zhang,Meiyu Gao,Qinwen Xiao,Zhaoqian Li,Haijuan Dong,Yuan Tian,Fengguo Xu,Yuxin Zhang
Dipeptides (DPs) have attracted more and more attention in many research fields due to their important biological functions and promising roles as disease biomarkers. However, the determination of DPs in biological samples is very challenging owing to the limited availability of commercial standards, high structure diversity, distinct physical and chemical characteristics, wide concentration range, and the extensive existence of isomers. In this study, a pseudotargeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) method coupled with chemical derivatization for the simultaneous analysis of 400 DPs and their constructing amino acids (AAs) in biospecimens is established. Dansyl chloride (Dns-Cl) chemical derivatization was introduced to provide characteristic MS fragments for annotation and improve the chromatographic separation of DP isomers. A retention time (RT) prediction model was constructed using 83 standards (63 DPs and 20 AAs) based on their quantitative structural retention relationship (QSRR) after the Dns-Cl labeling, which largely facilitated the annotation of the DPs without standards. Finally, we applied this method to investigate the profile change of DPs in a cisplatin-induced acute kidney injury (AKI) rat model. The established workflow provides a platform to profile DPs and expand our understanding of these little-studied metabolites.
研究领域:
分析化学
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代谢组学
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医学研究
✓ 已验证
DOI
PubMed
高影响因子
Bioanalysis
·
2025
·
IF 1.8
Xu Yan,Shuang Wang,Ying Li,Li Cui,Zhitu Zhu,Haiwen Liu,Lu Wang,Yanru Zhu,Furong Zhao,Ping Yang
Aims Omega-3 (n-3) and omega-6 (n-6) polyunsaturated fatty acids (PUFAs) are indispensable for human health. Notably, imbalanced levels of maternal PUFAs during pregnancy can exert lasting impacts on the developing fetus. There is an urgent need for a robust and rapid method that can simultaneously quantify multiple n-3 and n-6 PUFAs in plasma and adapt to large-scale clinical screening.Methods Sample preparative process consisted of non-derivatized alkali hydrolyzing and liquid–liquid extraction followed by reconstituting after being blown dry with nitrogen, and the total chromatographic run time was only 5.6 min.Results The LC-MS/MS method was validated according to current national and international guidelines. Acceptable reproducibility and accuracy were shown based on the intra-day precision was 1.79%–7.02%, the inter-day precision was 0.01%–5.63%, and the accuracy was 87.42%–102.78%. The correlation coefficients of linearity were >0.9930. All measured plasma individual PUFAs levels in pregnant women significantly increased, apart from eicosapentaenoic acid (EPA, C20:5n3) and n-6/n-3 PUFA ratio levels decreased were observed. The analysis performance is satisfactory and suitable for clinical routine detection.Conclusion This method could be a valuable tool for 10 kinds of n-3 and n-6 PUFAs nutritional assessment, supplementary guidance, and intervention during pregnancy.
研究领域:
临床医学
·
营养学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）