{"title":"Strobilanthes sarcorrhiza root phenolic extract prevent diabetic nephropathy in mice by regulating NF-κB/IL-1β signaling and glycerophospholipid metabolism","authors":"Rongchang Chen , Jiaping Fan , Yiwei Wu , Xueli Huang , Wenting Zhang , Yuyan Xu , Yunhan Zhang , Longyu Li , Chaojie Wang , Meng Yu , Yindi Zhu","doi":"10.1016/j.jpba.2024.116534","DOIUrl":"10.1016/j.jpba.2024.116534","url":null,"abstract":"<div><div><em>Strobilanthes sarcorrhiza</em>, a folk medicine from China, is known to treat kidney deficiency and lumbago. However, its protective effects and mechanisms against diabetic nephropathy (DN) remain unclear. This study aimed to investigate the effects and mechanisms of <em>Strobilanthes sarcorrhiza</em> root phenolic extract (CTS) on streptozotocin (STZ)-induced DN in mice. Firstly, the constituents in CTS were characterized by UPLC-QTOF-MS. Thirty-three constituents were identified, including 12 phenylethanoid glycosides and their derivatives, 14 phenylpropanoid glycosides derivatives, 6 polyphenols derivatives, and 1 other constituent. Then, utilizing the identified constituents of CTS, network pharmacology was used to anticipate potential pathways against DN. Thirty-two out of thirty-three constituents showed anti-DN activity; their mechanism of action was significantly linked to tumor-, glycosylation-, metabolism-related pathways, etc. Furthermore, the effectiveness of CTS against DN and its <em>in vivo</em> mechanism was assessed by combining immunohistochemistry, untargeted metabolomics, biochemical evaluation, and histopathological examination. The findings showed that CTS improved blood glucose and lipid levels in diabetic mice, reduced serum levels of ALT, CREA, UREA, IL-1β, and IL-17, decreased pathological damage and fibrosis in kidney tissue, and lowered the protein expression of VEGF, Laminin, TNF-α, and NF-κB in kidney tissue. Metabolomics results indicated that CTS alleviated DN mainly by regulating glycerophospholipid metabolism. To the best of our knowledge, this study is the first to report that <em>Strobilanthes sarcorrhiza</em> attenuates DN, potentially through the inhibition of the NF-κB pathway, leading to a reduction in the inflammatory response and fibrosis of renal tissue. These findings suggest that <em>Strobilanthes sarcorrhiza</em> could be a promising therapeutic agent for DN.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"253 ","pages":"Article 116534"},"PeriodicalIF":3.1,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yan Cao , Xiaoxue Yang , Pengliang Shi, Guozhong Niu, Suzhen Zhang, Zhengwei Gu, Qingmei Guo
{"title":"Tissue-specific chemical expression and quantitative analysis of bioactive components of Moutan Cortex by laser-microdissection combined with UPLC-Q-Orbitrap-MS technique","authors":"Yan Cao , Xiaoxue Yang , Pengliang Shi, Guozhong Niu, Suzhen Zhang, Zhengwei Gu, Qingmei Guo","doi":"10.1016/j.jpba.2024.116537","DOIUrl":"10.1016/j.jpba.2024.116537","url":null,"abstract":"<div><div>Moutan Cortex, is the root bark of <em>Paeonia suffruticosa</em> Andrews, which is classified into three specifications according to whether or not it is peeled and cored: Liandanpi, Guadanpi and whole root. In this study, the cork layer, cortex, phloem and xylem of <em>P. suffruticosa</em> fresh root were precisely separated by laser microdissection technique. UPLC-Q-Orbitrap-MS and UPLC-QQQ-MS techniques were used to analyse the differences in the chemical composition of different tissue parts of <em>P. suffruticosa</em> fresh root and Liandanpi, and to determine the optimal processing method of <em>P. suffruticosa</em> root. As a result, a total of 90 compounds were characterised, among which the cork layer had more types and higher contents of chemical constituents, and the xylem had fewer types and lower contents of chemical constituents. The proportion of xylem is larger, while the type and content of active ingredients is smaller. Therefore, the processing method of removing the wood core and retaining the cork bark can be used in the processing of Moutan Cortex. In this study, laser microdissection and ultra performance liquid chromatography-mass spectrometry were used to provide a theoretical basis for optimising the processing method of Moutan Cortex to enhance its pharmacological effects.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"253 ","pages":"Article 116537"},"PeriodicalIF":3.1,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jingru Song , Yanping Huang , Lu Liu , Dengcheng Hui , Zheng Wang , Dong Xie , Yulang Jiang , Hongyan Cao , Yancheng Dai , Guan Ye , Shibing Su , Mingmei Zhou , Qin Zhang , Mingyu Sun
{"title":"Integrated metabolomics and network pharmacology to explore the clinical efficacy and mechanism of Yinchenhao decoction combined with nucleoside analogues on chronic hepatitis B","authors":"Jingru Song , Yanping Huang , Lu Liu , Dengcheng Hui , Zheng Wang , Dong Xie , Yulang Jiang , Hongyan Cao , Yancheng Dai , Guan Ye , Shibing Su , Mingmei Zhou , Qin Zhang , Mingyu Sun","doi":"10.1016/j.jpba.2024.116513","DOIUrl":"10.1016/j.jpba.2024.116513","url":null,"abstract":"<div><div>Yinchenhao decoction (YCHD) is widely used in the treatment of damp-heat syndrome of chronic hepatitis B (CHB), but it remains unclear about the active compounds in YCHD and its potential mechanism for treating CHB. The purpose of this work is to evaluate the clinical efficacy of YCHD combined with nucleoside analogues (NAs) for the treatment of CHB. Besides, based on the exact clinical efficacy, we combined serum metabolomics and network pharmacology to screen differential metabolites and related pathways regulated by YCHD to investigate the possible mechanism for treating CHB. It revealed that NAs plus YCHD could significantly improve alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, increase HBV-DNA negative rate (<em>P</em><0.05), reduce the levels of inflammatory factors and LSM (both <em>P</em><0.05), regulate lipids (<em>P</em><0.05), and improve the symptoms of traditional Chinese medicine (TCM) (<em>P</em><0.05) in CHB patients. YCHD was relatively safe. It showed 30 active compounds including chlorogenic acid, geniposide, emodin, quercetin, kaempferol, β-sitosterol and aloe emodin, and 115 key targets which were related to the regulation of lipids and reduction of oxidative stress related to the effect of YCHD in CHB in the network pharmacology analysis. We found 9 core targets and 4 key metabolites according to metabolomics, which were partly consistent with the network pharmacology findings. It proved that network pharmacology combined with metabolomics can well explain the “multi-component-multi-target” mechanism of complex TCM.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"253 ","pages":"Article 116513"},"PeriodicalIF":3.1,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jaime Millán-Santiago, Carlos Calero-Cañuelo, Rafael Lucena, Soledad Cárdenas
{"title":"Coupling microextraction techniques with substrate spray mass spectrometry, towards a faster analysis of biological samples","authors":"Jaime Millán-Santiago, Carlos Calero-Cañuelo, Rafael Lucena, Soledad Cárdenas","doi":"10.1016/j.jpba.2024.116535","DOIUrl":"10.1016/j.jpba.2024.116535","url":null,"abstract":"<div><div>Direct coupling sample preparation with mass spectrometry has risen as a reliable analytical strategy in bioanalysis as it provides a high sample throughput. This approach avoids an exhaustive separation step, thus being cost-effective compared to the traditional analytical workflow. The selectivity and sensitivity levels rely on the mass spectrometric analysis and the appropriate selection of the sample preparation. Miniaturized extraction techniques have demonstrated particular utility in this coupling thanks to their ability to pre-concentrate the target analytes while removing many of the matrix components. This article reviews the main developments in combining microextraction techniques with mass spectrometry based on electrospray ionization, a consolidated ionization technique in bioanalysis. The article aims to provide an overview of the potential of these techniques by describing the most significant examples. The different approaches are classified according to the materials or devices used to perform the extraction and analysis.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"253 ","pages":"Article 116535"},"PeriodicalIF":3.1,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yanni Xue , Changling Lv , Lu Jin , Di Tan , Dingyu Wu , Fang Peng
{"title":"Study on the mechanism of Xinmailong injection against chronic heart failure based on transcriptomics and proteomics","authors":"Yanni Xue , Changling Lv , Lu Jin , Di Tan , Dingyu Wu , Fang Peng","doi":"10.1016/j.jpba.2024.116529","DOIUrl":"10.1016/j.jpba.2024.116529","url":null,"abstract":"<div><div>Xinmailong (XML), a traditional Chinese medicine derived from Periplaneta americana, is commonly used in China to treat chronic heart failure (CHF). However, its pharmacological mechanism remains unclear. In our research, we employed Doxorubicin (Dox) to create a CHF animal model and administered XML treatment to investigate the pharmacological effects of XML on CHF rats by combining transcriptomic and proteomic analyses. XML improved dox-induced CHF and improved cardiac function, and a joint multi-omics analysis demonstrated that it reduced cardiomyocyte fibrosis during CHF. There is further evidence that XML may alleviate cardiomyocyte fibrosis through its effects on the cGMP-PKG signaling pathway or by reducing the expression levels of COL1A1, COL3A1, MMP9, and CXCR2. In this study, the effects of XML on rats with CHF are examined at the transcriptional and protein levels, as well as its mechanism and mode of action in treating CHF. There may be novel therapeutic targets or clinical indications for XML-based CHF therapy resulting from the study's identification of significant differential genes and signaling pathways.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"253 ","pages":"Article 116529"},"PeriodicalIF":3.1,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abdelaziz Moutcine , Charaf Laghlimi , Younes Ziat , Soumia El Bahraoui , Hamza Belkhanchi , Ahmed Jouaiti
{"title":"Advanced design of chemically modified electrodes for the electrochemical analysis of uric acid and xanthine","authors":"Abdelaziz Moutcine , Charaf Laghlimi , Younes Ziat , Soumia El Bahraoui , Hamza Belkhanchi , Ahmed Jouaiti","doi":"10.1016/j.jpba.2024.116536","DOIUrl":"10.1016/j.jpba.2024.116536","url":null,"abstract":"<div><div>This study reviews advances in chemical detection methods applied to the metabolic products known as uric acid (UA) and xanthine (XA), which are residues of purine metabolism, with XA being an important intermediate preceding UA. UA and XA play crucial roles in maintaining physiological homeostasis in organisms. Chemical modification of electrodes is a widely used method to address the issues of poor sensitivity and selectivity encountered with bare electrodes. This article reviews various materials commonly used to modify electrode surfaces for the detection of uric acid and xanthine, focusing on properties that enhance electrocatalytic activity. We highlight recent trends in detecting these compounds using electrochemical methods with microfabricated devices and explore cutting-edge modification techniques involving novel nanomaterials, carbon derivatives, metallic nanoparticles, and polymers. The review includes a comparative analysis of these materials, addressing their strengths, limitations, and recent advancements, such as in carbon-based materials and metal-organic frameworks (MOFs). Finally, we critically examine the challenges and future prospects of electrochemical detection of UA and XA in real samples, offering strategies to address these issues.</div><div>The challenges associated with determination of UA and XA in real samples are also discussed.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"253 ","pages":"Article 116536"},"PeriodicalIF":3.1,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142546062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Péter P. Lakatos , Zsuzsanna Ignáth , Orsolya Csernák , Imre Boldizsár , Éva Szökő , Tamás Tábi
{"title":"Separation of tolperisone and its degradation products by a dual cyclodextrin capillary electrophoresis system to study their potential role in allergic events","authors":"Péter P. Lakatos , Zsuzsanna Ignáth , Orsolya Csernák , Imre Boldizsár , Éva Szökő , Tamás Tábi","doi":"10.1016/j.jpba.2024.116532","DOIUrl":"10.1016/j.jpba.2024.116532","url":null,"abstract":"<div><div>Tolperisone is a centrally acting muscle relaxant that has been used for the treatment of post-stroke spasticity and low back pain. Recently, the safety of tolperisone pharmaceutical products has been reassessed due to growing concerns over allergic adverse events. Reactive degradants of tolperisone may be responsible for these hypersensitivity reactions. By forming adducts with proteins, they may act as haptens that could evoke allergic reactions. The objective of this study was to examine the presence of these degradants in tolperisone pharmaceutical products and to assess their reactivity to elucidate their possible role in the pro-allergic effect of tolperisone. For this purpose, capillary electrophoresis UV detection (CE-UV) method was developed and validated for the quantification of degradants. A dual cyclodextrin system was applied to achieve the appropriate migration order enabling the analysis of 2-methyl-1-(4-methylphenyl)prop-2-en-1-one (MMP) and 1-(4-methylphenyl)propan-1-one (MMPO) in the presence of high concentrations of tolperisone. MMP was identified as the main degradant in forced degradation tests of the active pharmaceutical ingredient. Differences in MMP content of tolperisone products by different manufacturers have also been found, highlighting the role of formulation in their stability. High reactivity of MMP was demonstrated as rapid and almost complete adduct formation with cysteine was found. This degradant thus might be responsible for the allergic adverse effects of tolperisone even when it is present in trace amounts in tablets by readily reacting with proteins <em>in vivo</em>.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"252 ","pages":"Article 116532"},"PeriodicalIF":3.1,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sachin Chaturvedi, Nikhil Titkare, Nitish Sharma, Ravi P. Shah
{"title":"Characterization of disulfide bridges containing cyclic peptide Linaclotide and its degradation products by using LC-HRMS/MS","authors":"Sachin Chaturvedi, Nikhil Titkare, Nitish Sharma, Ravi P. Shah","doi":"10.1016/j.jpba.2024.116533","DOIUrl":"10.1016/j.jpba.2024.116533","url":null,"abstract":"<div><div>Linaclotide (LINA) is a first-in-class guanylate cyclase agonist used for treating irritable bowel syndrome with constipation (IBS-C) and chronic idiopathic constipation. Stress degradation studies were performed to examine LINA's intrinsic stability, adhering to International Council for Harmonisation of Technical ICH) guidelines Q1A (R2). The current study endeavours to elucidate the stability behavior of LINA by exposing various stress conditions. A simple LC method was developed for effective separation of all LINA degradation products using a Waters Symmetry C18 column (150 ×4.6 mm, 3.5 µm) as the stationary phase. The generated degradation products were identified and characterized by using high-resolution mass spectrometry (LC-HRMS), MS/MS studies. The mechanistic fragmentation pathway for the seven degradation products was established and the chemical structure for the identified degradation products was elucidated. LINA was susceptible to degrade under acidic, basic, neutral, photolytic, and oxidative conditions. A total of three Pseudo DPs, DP-1, DP-2, and DP-3, were formed under acidic conditions while using methanol as the co-solvent. Additionally, degradation products (DPs) were identified: DP-4 formed under basic stress condition and DP-5 under neutral, thermal, and photolytic conditions. Furthermore, DP-6 and DP-7 were formed under oxidative stress condition. This study established the mechanistic fragmentation pathways and elucidated the chemical structures of the degradation products, offering valuable insights for generics and novel formulation drug development.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"252 ","pages":"Article 116533"},"PeriodicalIF":3.1,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yue Feng , Zijian Sun , Huan Zhang , Zhao Wang , Lichao Wang , Hui Ye , Xiaojing Zhang , Zhuomin Yin , Juan Ni , Jingkui Tian , Hanmei Lou , Xiaojuan Lv , Wei Zhu
{"title":"Plasma-based proteomic and metabolomic characterization of lung and lymph node metastases in cervical cancer patients","authors":"Yue Feng , Zijian Sun , Huan Zhang , Zhao Wang , Lichao Wang , Hui Ye , Xiaojing Zhang , Zhuomin Yin , Juan Ni , Jingkui Tian , Hanmei Lou , Xiaojuan Lv , Wei Zhu","doi":"10.1016/j.jpba.2024.116521","DOIUrl":"10.1016/j.jpba.2024.116521","url":null,"abstract":"<div><div>Metastasis is the leading cause of mortality in cervical cancer (CC), with a particular prevalence of lymph node and lung metastases. Patients with CC who have developed distant metastases typically face a poor prognosis, and there is a scarcity of non-invasive strategies for predicting CC metastasis. In this study, we utilized label-free proteomics and untargeted metabolomics to analyze plasma samples from 25 non-metastatic, 14 with lung metastasis, and 15 with lymph node metastasis CC patients. Pathway enrichment analysis revealed a shared inflammatory process between the two metastatic groups, while the central carbon metabolism in cancer showed distinct features in the lung metastasis cohort. Additionally, cholesterol metabolism, hypoxia-inducible factor 1, and ferroptosis signaling pathways were specifically altered in the lymph node metastasis group. Utilizing the receiver operating characteristic curve analysis and Random Forest algorithm, we identified two distinct biomarker panels for the prediction of lung metastasis and lymph node metastasis, respectively. The lung metastasis panel includes properdin, neural cell adhesion molecule 1, and keratin 6 A, whereas the lymph node metastasis panel consists of quiescin sulfhydryl oxidase 1, paraoxonase 1, and keratin 6 A. Each panel exhibited significant diagnostic potential, with high area under the curve (AUC) values for lung metastasis (training set: 0.989, testing set: 0.789) and lymph node metastasis (training set: 0.973, testing set: 0.900). This study conducted an integrated proteomic and metabolomic analysis to clarify the factors contributing to lung and lymph node metastases in CC and has successfully established two biomarker panels for their prediction.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"253 ","pages":"Article 116521"},"PeriodicalIF":3.1,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kasey L. Hill , Nicole L. Abbott , Joo Young Na , Michelle Rudek , Kathleen Moore , Eudocia Q. Lee , Mitch A. Phelps
{"title":"Assay for the quantification of abemaciclib, its metabolites, and olaparib in human plasma by liquid chromatography-tandem mass spectrometry","authors":"Kasey L. Hill , Nicole L. Abbott , Joo Young Na , Michelle Rudek , Kathleen Moore , Eudocia Q. Lee , Mitch A. Phelps","doi":"10.1016/j.jpba.2024.116531","DOIUrl":"10.1016/j.jpba.2024.116531","url":null,"abstract":"<div><div>An isotope-dilution bioanalytical assay for abemaciclib and its metabolites in combination with olaparib was developed and validated in human plasma K2 EDTA. For the quantitative assay, human plasma samples (or human plasma QC samples) were spiked with internal standard solution before a simple protein precipitation with methanol. The extract was injected onto a liquid chromatography-tandem mass spectrometry (LC-MS/MS) instrument where it was chromatographically separated by a polar end-capped reversed phase column and guard using gradient elution with water and methanol both modified with 0.2 % formic acid (v/v) as the mobile phases. The analytes and internal standards were measured by heated electrospray ionization (HESI) in positive polarity using selected reaction monitoring (SRM) on a triple quadrupole mass spectrometer. The assay was validated for linear ranges as follows: 0.4 – 1000 nM abemaciclib, 0.35 – 1000 nM M2 and M18, 0.5 – 1000 nM M20, and 0.75 – 1000 nM olaparib. The inter-day or between day precision for the quality controls (n = 18) was < 13 % and the accuracy was ± 12 %, for all analytes, including the lower limit of quantification (LLOQ). The intra-day or within day precision for the quality controls (n = 6) was ≤ 11 % and the accuracy was ± 12 % for low, mid, and high and < 19 % at LLOQ. The recovery in human plasma was determined to be between 92 % and 102 % for all analytes spanning the linear range. The validated, bioanalytical quantitative assay was designed to measure abemaciclib, its metabolites, and olaparib for pharmacokinetic evaluation of patients in clinical trials for breast, brain, and ovarian cancers.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"253 ","pages":"Article 116531"},"PeriodicalIF":3.1,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}