Journal of Pharmaceutical Analysis最新文献

{"title":"In vivo solid phase microextraction for therapeutic monitoring and pharmacometabolomic fingerprinting of lung during in vivo lung perfusion of FOLFOX","authors":"Nikita Looby ,&nbsp;Anna Roszkowska ,&nbsp;Miao Yu ,&nbsp;German Rios-Gomez ,&nbsp;Mauricio Pipkin ,&nbsp;Barbara Bojko ,&nbsp;Marcelo Cypel ,&nbsp;Janusz Pawliszyn","doi":"10.1016/j.jpha.2023.04.005","DOIUrl":"10.1016/j.jpha.2023.04.005","url":null,"abstract":"<div><p>In vivo lung perfusion (IVLP) is a novel isolated lung technique developed to enable the local, in situ administration of high-dose chemotherapy to treat metastatic lung cancer. Combination therapy using folinic acid (FOL), 5-fluorouracil (F), and oxaliplatin (OX) (FOLFOX) is routinely employed to treat several types of solid tumours in various tissues. However, F is characterized by large interpatient variability with respect to plasma concentration, which necessitates close monitoring during treatments using of this compound. Since plasma drug concentrations often do not reflect tissue drug concentrations, it is essential to utilize sample-preparation methods specifically suited to monitoring drug levels in target organs. In this work, in vivo solid-phase microextraction (in vivo SPME) is proposed as an effective tool for quantitative therapeutic drug monitoring of FOLFOX in porcine lungs during pre-clinical IVLP and intravenous (IV) trials. The concomitant extraction of other endogenous and exogenous small molecules from the lung and their detection via liquid chromatography coupled to high resolution mass spectrometry (LC-HRMS) enabled an assessment of FOLFOX's impact on the metabolomic profile of the lung and revealed the metabolic pathways associated with the route of administration (IVLP vs. IV) and the therapy itself. This study also shows that the immediate instrumental analysis of metabolomic samples is ideal, as long-term storage at −80 °C results in changes in the metabolite content in the sample extracts.</p></div>","PeriodicalId":16737,"journal":{"name":"Journal of Pharmaceutical Analysis","volume":"13 10","pages":"Pages 1195-1204"},"PeriodicalIF":8.8,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48706280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Albumin-bound kynurenic acid is an appropriate endogenous biomarker for assessment of the renal tubular OATs-MRP4 channel","authors":"Yanrong Ma ,&nbsp;Fenglin Ran ,&nbsp;Mingyan Xin ,&nbsp;Xueyan Gou ,&nbsp;Xinyi Wang ,&nbsp;Xinan Wu","doi":"10.1016/j.jpha.2023.05.007","DOIUrl":"10.1016/j.jpha.2023.05.007","url":null,"abstract":"<div><p>Renal tubular secretion mediated by organic anion transporters (OATs) and the multidrug resistance-associated protein 4 (MRP4) is an important means of drug and toxin excretion. Unfortunately, there are no biomarkers to evaluate their function. The aim of this study was to identify and characterize an endogenous biomarker of the renal tubular OATs-MRP4 channel. Twenty-six uremic toxins were selected as candidate compounds, of which kynurenic acid was identified as a potential biomarker by assessing the protein-binding ratio and the uptake in OAT1-, OAT3-, and MRP4-overexpressing cell lines. OAT1/3 and MRP4 mediated the transcellular vectorial transport of kynurenic acid in vitro. Serum kynurenic acid concentration was dramatically increased in rats treated with a rat OAT1/3 (rOAT1/3) inhibitor and in rOAT1/3 double knockout (rOAT1/3^−/−) rats, and the renal concentrations were markedly elevated by the rat MRP4 (rMRP4) inhibitor. Kynurenic acid was not filtered at the glomerulus (99% of albumin binding), and was specifically secreted in renal tubules through the OAT1/3-MRP4 channel with an appropriate affinity (<em>K</em>_m) (496.7 μM and 382.2 μM for OAT1 and OAT3, respectively) and renal clearance half-life (<em>t</em>_1/2) in vivo (3.7 ± 0.7 h). There is a strong correlation in area under the plasma drug concentration-time curve (AUC_{0–<em>t</em>}) between cefmetazole and kynurenic acid, but not with creatinine, after inhibition of rOATs. In addition, the phase of increased kynurenic acid level is earlier than that of creatinine in acute kidney injury process. These results suggest that albumin-bound kynurenic acid is an appropriate endogenous biomarker for adjusting the dosage of drugs secreted by this channel or predicting kidney injury.</p></div>","PeriodicalId":16737,"journal":{"name":"Journal of Pharmaceutical Analysis","volume":"13 10","pages":"Pages 1205-1220"},"PeriodicalIF":8.8,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44167711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Monoclonal antibody targeting mu-opioid receptor attenuates morphine tolerance via enhancing morphine-induced receptor endocytosis","authors":"Jia-Jia Zhang ,&nbsp;Chang-Geng Song ,&nbsp;Miao Wang ,&nbsp;Gai-Qin Zhang ,&nbsp;Bin Wang ,&nbsp;Xi Chen ,&nbsp;Peng Lin ,&nbsp;Yu-Meng Zhu ,&nbsp;Zhi-Chuan Sun ,&nbsp;Ya-Zhou Wang ,&nbsp;Jian-Li Jiang ,&nbsp;Ling Li ,&nbsp;Xiang-Min Yang ,&nbsp;Zhi-Nan Chen","doi":"10.1016/j.jpha.2023.06.008","DOIUrl":"10.1016/j.jpha.2023.06.008","url":null,"abstract":"<div><p>Morphine is a frequently used analgesic that activates the mu-opioid receptor (MOR), which has prominent side effects of tolerance. Although the inefficiency of morphine in inducing the endocytosis of MOR underlies the development of morphine tolerance, currently, there is no effective therapy to treat morphine tolerance. In the current study, we aimed to develop a monoclonal antibody (mAb) precisely targeting MOR and to determine its therapeutic efficacy on morphine tolerance and the underlying molecular mechanisms. We successfully prepared a mAb targeting MOR, named 3A5C7, by hybridoma technique using a strategy of deoxyribonucleic acid immunization combined with cell immunization, and identified it as an immunoglobulin G mAb with high specificity and affinity for MOR and binding ability to antigens with spatial conformation. Treatment of two cell lines, HEK293T and SH-SY5Y, with 3A5C7 enhanced morphine-induced MOR endocytosis via a G protein-coupled receptor kinase 2 (GRK2)/β-arrestin2-dependent mechanism, as demonstrated by immunofluorescence staining, flow cytometry, Western blotting, coimmunoprecipitation, and small interfering ribonucleic acid (siRNA)-based knockdown. This mAb also allowed MOR recycling from cytoplasm to plasma membrane and attenuated morphine-induced phosphorylation of MOR. We established an in vitro morphine tolerance model using differentiated SH-SY5Y cells induced by retinoic acid. Western blot, enzyme-linked immunosorbent assays, and siRNA-based knockdown revealed that 3A5C7 mAb diminished hyperactivation of adenylate cyclase, the in vitro biomarker of morphine tolerance, via the GRK2/β-arrestin2 pathway. Furthermore, in vivo hotplate test demonstrated that chronic intrathecal administration of 3A5C7 significantly alleviated morphine tolerance in mice, and withdrawal jumping test revealed that both chronic and acute 3A5C7 intrathecal administration attenuated morphine dependence. Finally, intrathecal electroporation of silencing short hairpin RNA illustrated that the in vivo anti-tolerance and anti-dependence efficacy of 3A5C7 was mediated by enhanced morphine-induced MOR endocytosis via GRK2/β-arrestin2 pathway. Collectively, our study provided a therapeutic mAb, 3A5C7, targeting MOR to treat morphine tolerance, mediated by enhancing morphine-induced MOR endocytosis. The mAb 3A5C7 demonstrates promising translational value to treat clinical morphine tolerance.</p></div>","PeriodicalId":16737,"journal":{"name":"Journal of Pharmaceutical Analysis","volume":"13 10","pages":"Pages 1135-1152"},"PeriodicalIF":8.8,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43084226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SPME as a green sample-preparation technique for the monitoring of phytocannabinoids and endocannabinoids in complex matrices","authors":"Katarzyna Woźniczka ,&nbsp;Paweł Konieczyński ,&nbsp;Alina Plenis ,&nbsp;Tomasz Bączek ,&nbsp;Anna Roszkowska","doi":"10.1016/j.jpha.2023.06.014","DOIUrl":"10.1016/j.jpha.2023.06.014","url":null,"abstract":"<div><p>The endocannabinoid system (ECS), particularly its signaling pathways and ligands, has garnered considerable interest in recent years. Along with clinical work investigating the ECS’ functions, including its role in the development of neurological and inflammatory conditions, much research has focused on developing analytical protocols enabling the precise monitoring of the levels and metabolism of the most potent ECS ligands: exogenous phytocannabinoids (PCs) and endogenous cannabinoids (endocannabinoids, ECs). Solid-phase microextraction (SPME) is an advanced, non-exhaustive sample-preparation technique that facilitates the precise and efficient isolation of trace amounts of analytes, thus making it appealing for the analysis of PCs and ECs in complex matrices of plant and animal/human origin. In this paper, we review recent forensic medicine and toxicological studies wherein SPME has been applied to monitor levels of PCs and ECs in complex matrices, determine their effects on organism physiology, and assess their role in the development of several diseases.</p></div>","PeriodicalId":16737,"journal":{"name":"Journal of Pharmaceutical Analysis","volume":"13 10","pages":"Pages 1117-1134"},"PeriodicalIF":8.8,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48550976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Simultaneously quantifying hundreds of acylcarnitines in multiple biological matrices within ten minutes using ultrahigh-performance liquid-chromatography and tandem mass spectrometry","authors":"Jingxian Zhang, Qinsheng Chen, Lianglong Zhang, Biru Shi, Men Yu, Qingxia Huang, Huiru Tang","doi":"10.1016/j.jpha.2023.10.004","DOIUrl":"https://doi.org/10.1016/j.jpha.2023.10.004","url":null,"abstract":"Acylcarnitines are metabolic intermediates of fatty acids and branched-chain amino acids having vital biofunctions and pathophysiological significances. Here, we developed a high-throughput method for quantifying hundreds of acylcarnitines in one run using ultrahigh performance liquid chromatography and tandem mass spectrometry. This enabled simultaneous quantification of 1136 acylcarnitines (C0–C26) within 10-min with good sensitivity (limit of detection (LOD) < 0.7 fmol), linearity (correlation coefficient > 0.992), accuracy (relative error < 20%), precision (coefficient of variation (CV), CV < 15%), stability (CV < 15%), and inter-technician consistency (CV < 20%, n = 6). We also established a quantitative structure-retention relationship (goodness of fit > 0.998) for predicting retention time (tR) of acylcarnitines with no standards and built a database of their multiple reaction monitoring parameters (tR, ion-pairs, collision energy). Furthermore, we quantified 514 acylcarnitines in human plasma and urine and mouse kidney, liver, heart, lung, muscle. This provides a rapid method for quantifying acylcarnitines in multiple biological matrices.","PeriodicalId":16737,"journal":{"name":"Journal of Pharmaceutical Analysis","volume":"7 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135850193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of different degrees of processed Ginger using GC-IMS combined with machine learning","authors":"Shuang Liu, Hongjing Dong, Minmin Zhang, Wei Geng, Xiao Wang","doi":"10.1016/j.jpha.2023.10.005","DOIUrl":"https://doi.org/10.1016/j.jpha.2023.10.005","url":null,"abstract":"• GC-IMS can analyze VOCs in different ginger processed products nondestructively and quickly • Nine indicator compounds are uncovered to distinguish different grades of processing ginger • Three machine learning models were built, with an accuracy of > 90% • These models were successfully validated in testing set","PeriodicalId":16737,"journal":{"name":"Journal of Pharmaceutical Analysis","volume":"66 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136094625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protective effects of dioscin against Parkinson's disease via regulating bile acid metabolism through remodeling gut microbiome/GLP-1 signaling","authors":"Zhang Mao ,&nbsp;Haochen Hui ,&nbsp;Xuerong Zhao ,&nbsp;Lina Xu ,&nbsp;Yan Qi ,&nbsp;Lianhong Yin ,&nbsp;Liping Qu ,&nbsp;Lan Han ,&nbsp;Jinyong Peng","doi":"10.1016/j.jpha.2023.06.007","DOIUrl":"10.1016/j.jpha.2023.06.007","url":null,"abstract":"<div><p>It is necessary to explore potent therapeutic agents via regulating gut microbiota and metabolism to combat Parkinson's disease (PD). Dioscin, a bioactive steroidal saponin, shows various activities. However, its effects and mechanisms against PD are limited. In this study, dioscin dramatically alleviated neuroinflammation and oxidative stress, and restored the disorders of mice induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). 16 S rDNA sequencing assay demonstrated that dioscin reversed MPTP-induced gut dysbiosis to decrease <em>Firmicutes</em>-to-<em>Bacteroidetes</em> ratio and the abundances of <em>Enterococcus</em>, <em>Streptococcus</em>, <em>Bacteroides</em> and <em>Lactobacillus genera</em>, which further inhibited bile salt hydrolase (BSH) activity and blocked bile acid (BA) deconjugation. Fecal microbiome transplantation test showed that the <em>anti</em>-PD effect of dioscin was gut microbiota-dependent. In addition, non-targeted fecal metabolomics assays revealed many differential metabolites in adjusting steroid biosynthesis and primary bile acid biosynthesis. Moreover, targeted bile acid metabolomics assay indicated that dioscin increased the levels of ursodeoxycholic acid, tauroursodeoxycholic acid, taurodeoxycholic acid and β-muricholic acid in feces and serum. In addition, ursodeoxycholic acid administration markedly improved the protective effects of dioscin against PD in mice. Mechanistic test indicated that dioscin significantly up-regulated the levels of takeda G protein-coupled receptor 5 (TGR5), glucagon-like peptide-1 receptor (GLP-1R), GLP-1, superoxide dismutase (SOD), and down-regulated NADPH oxidases 2 (NOX2) and nuclear factor-kappaB (NF-κB) levels. Our data indicated that dioscin ameliorated PD phenotype by restoring gut dysbiosis and regulating bile acid-mediated oxidative stress and neuroinflammation via targeting GLP-1 signal in MPTP-induced PD mice, suggesting that the compound should be considered as a prebiotic agent to treat PD in the future.</p></div>","PeriodicalId":16737,"journal":{"name":"Journal of Pharmaceutical Analysis","volume":"13 10","pages":"Pages 1153-1167"},"PeriodicalIF":8.8,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47207348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Platycodin D inhibits angiogenic vascular mimicry in NSCLC by regulating the eIF4E-mediated RNA methylome","authors":"Shuyu Zheng, Yanlin Xin, Jiamin Lin, Zejuan Xie, Keyu Cheng, Shanshan Wang, Wenli Lu, Hao Yang, Tianming Lu, Jun Li, Ruogu Qi, Yuanyuan Guo","doi":"10.1016/j.jpha.2023.10.003","DOIUrl":"https://doi.org/10.1016/j.jpha.2023.10.003","url":null,"abstract":"• The m7G-lncRNAs were identified through whole transcriptome-seq of PD and RIP validation. • The anti-VM effect of PD on NSCLC was investigated both in vivo and in vitro. • The synergistic effect was found in combinational use of PD and eIF4E inhibitor on NSCLC via destabilization of EGFR.","PeriodicalId":16737,"journal":{"name":"Journal of Pharmaceutical Analysis","volume":"275 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135761665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The “depict” strategy for discovering new compounds in complex matrices: Lycibarbarspermidines as a case","authors":"Chen Han, Zhixin Zhang, Zhiyang Feng, Chuanjia Zhai, Xuejiao Li, Yulian Shi, Xiang Li, Miao Li, Ying Wang, Gan Luo, Xiaoyan Gao","doi":"10.1016/j.jpha.2023.10.007","DOIUrl":"https://doi.org/10.1016/j.jpha.2023.10.007","url":null,"abstract":"The comprehensive detection and identification of active ingredients in complex matrices is a crucial challenge. Liquid chromatography coupled with high-resolution mass spectrometry (LC-HRMS) is the most prominent analytical platform for the exploration of novel active compounds from complex matrices. However, the LC-HRMS-based analysis workflow suffers from several bottleneck issues, such as trace content of target compounds, limited acquisition for fragment information, and uncertainty in interpreting relevant MS2 spectra. Lycibarbarspermidines are vital antioxidant active ingredients in Lycii Fructus, while the reported structures are merely focused on dicaffeoylspermidines due to their low content. To comprehensively detect the new structures of lycibarbarspermidine derivatives, a “depict” strategy was developed in this study. First, potential new lycibarbarspermidine derivatives were designed according to the biosynthetic pathway, and a comprehensive database was established, which enlarged the coverage of lycibarbarspermidine derivatives. Second, the polarity-oriented sample preparation of potential new compounds increased the concentration of the target compounds. Third, the construction of the molecular network based on the fragmentation pathway of lycibarbarspermidine derivatives broadened the comprehensiveness of identification. Finally, the weak response signals were captured by data-dependent scanning (DDA) followed by parallel reaction monitoring (PRM), and the efficiency of acquiring MS2 fragment ions of target compounds was significantly improved. Based on the integrated strategy above, 210 lycibarbarspermidine derivatives were detected and identified from Lycii Fructus, and in particular, 170 potential new compounds were structurally characterized. The integrated strategy improved the sensitivity of detection and the coverage of low-response components, and it is expected to be a promising pipeline for discovering new compounds.","PeriodicalId":16737,"journal":{"name":"Journal of Pharmaceutical Analysis","volume":"58 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136094464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced identification and localization of metabolites in Scutellariae Radix using ion mobility enabled MALDI-Q-TOF/MS imaging","authors":"Lixing Nie, Lieyan Huang, Xiaofei Jia, Shuai Kang, Lingwen Yao, Yanpei Wu, Hao Yuan, Yongli Liu, Feng Wei, Hongyu Jin, Xiang Li, Shuangcheng Ma","doi":"10.1016/j.jpha.2023.09.018","DOIUrl":"https://doi.org/10.1016/j.jpha.2023.09.018","url":null,"abstract":"• MALDI-IM-MS localization of metabolites in Scutellariae Radix was conducted for the first time. • Mobility- m / z plot offered distinct separation of endogenous metabolites from matrix. • Exclusive trend line enabled more selective characterization of flavonoids.","PeriodicalId":16737,"journal":{"name":"Journal of Pharmaceutical Analysis","volume":"2014 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134934307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}