Journal of pharmaceutical and biomedical analysis最新文献

{"title":"Rapid quality evaluation of moutan cortex (Paeonia suffruticosa Andrews) by near-infrared spectroscopy and bionic swarm intelligent optimization algorithm","authors":"Ying Qiao ,&nbsp;Yatong Kang ,&nbsp;Tingze Long ,&nbsp;Han Yi ,&nbsp;Feng Wang ,&nbsp;Chao Chen","doi":"10.1016/j.jpba.2025.116822","DOIUrl":"10.1016/j.jpba.2025.116822","url":null,"abstract":"<div><div>Moutan Cortex (MC), recognized as a traditional Chinese medicinal herb, possesses significant therapeutic properties. The existing quality assessment method only measures the content of one component in MC, which is obviously not comprehensive enough. Besides, the determination process is time-consuming and laborious.Thus, this article presents a novel approach for the rapid, precise, and efficient quality assessment of MC based on near-infrared spectroscopy (NIR) technology in combination with the bionic swarm intelligent optimization algorithms. First, MC samples were collected and acquired with the NIR spectra in diffuse reflectance mode. Second, the content of paeonol, paeoniflorin, and gallic acid in MC was determined by high-performance liquid chromatography, and the content of total flavonoids and phenols was determined by UV–visible spectrophotometry. Afterward, all the measured content was analyzed in correlation with the NIR spectra of MC, and the partial least squares regression method was utilized to build the models. Especially, to improve the models’ performance, five famous bionic swarm intelligent optimization algorithms were investigated to perform the wavelength selection. As a result, the models’ performance was significantly enhanced. The coefficient of determination (<em>R</em>^<em>2</em>) &gt; 0.9 and residual prediction deviation (<em>RPD</em>) &gt; 3 were observed on the calibration set and the prediction set. Thus, we believe that bionic swarm intelligent optimization algorithms have the potential to enhance the performance of quantitative models considerably, which offers substantial support for the quality assessment of MC and shows promising applications in the domain of NIR analysis.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"260 ","pages":"Article 116822"},"PeriodicalIF":3.1,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143674013","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}

{"title":"Letter to Editor: Critical commentary on the study of Siddig et al: Pharmacovigilance of drug-drug interactions: A pharmacokinetic study on the combined oral administration of lurasidone and clozapine in rats by using LC-MS/MS","authors":"Jan Juřica","doi":"10.1016/j.jpba.2025.116799","DOIUrl":"10.1016/j.jpba.2025.116799","url":null,"abstract":"","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"260 ","pages":"Article 116799"},"PeriodicalIF":3.1,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143674007","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}

{"title":"Deciphering the mechanism of Annona muricata leaf extract in alloxan-nicotinamide-induced diabetic rat model with 1H-NMR-based metabolomics approach","authors":"Siti Norliyana Zubaidi ,&nbsp;Pei Lou Wong ,&nbsp;Wasim S.M. Qadi ,&nbsp;Esraa Adnan Dawoud Dawoud ,&nbsp;Hamizah Shahirah Hamezah ,&nbsp;Syarul Nataqain Baharum ,&nbsp;Faidruz Azura Jam ,&nbsp;Faridah Abas ,&nbsp;Andres Moreno ,&nbsp;Ahmed Mediani","doi":"10.1016/j.jpba.2025.116806","DOIUrl":"10.1016/j.jpba.2025.116806","url":null,"abstract":"<div><div>The leaves of <em>Annona muricata</em> Linn. have long been utilized in traditional medicine for diabetes treatment, and there is no study that has employed a metabolomics approach to investigate the plant's effects in managing the disease. We aimed to explore the antidiabetic effects of the standardised <em>A. muricata</em> leaf extract on diabetes-induced rats by alloxan monohydrate (Ax) and nicotinamide (NA) using a proton nuclear magnetic resonance (¹H-NMR)-based metabolomics approach. Absolute quantification was performed on the leaf extract using ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Two different doses of the extract were administered orally for four weeks to diabetic rats induced with Ax + NA, and physical evaluations, biochemical analyses, and ¹H-NMR metabolomics of urine and serum were assessed. The results showed that quercetin 3-rutinoside was the most abundant compound in the 80 % ethanolic extract of <em>A. muricata</em> leaf. The induction of type 2 diabetes mellitus (T2DM) in the rat model was confirmed by the clear metabolic distinction between normal rats, diabetic rats, and metformin-treated diabetic rats. The low-dose of <em>A. muricata</em> leaf extract (200 mg/kg) was found to exhibit better results, significantly reducing serum urea levels in diabetic rats, with effects comparable to those of metformin. Additionally, metabolite analysis from ¹H-NMR metabolomics of serum and urine showed a slight shift toward normal metabolic profiles in the treated diabetic rats. Pathway analysis revealed alterations in the tricarboxylic acid cycle (TCA), pyruvate metabolism, and glycolysis/gluconeogenesis pathways in the diabetic rat model, which were improved following treatment with the <em>A. muricata</em> leaf extract. Overall, this study provides scientific support for its traditional use in diabetes management and offers new insights into the underlying molecular mechanisms.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"260 ","pages":"Article 116806"},"PeriodicalIF":3.1,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143637173","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}

{"title":"Elucidating the mechanisms of Shenwu Capsule in improving the cognitive decline in aging based on the UPLC-Q-TOF-MS, network pharmacology, and experimental validation","authors":"Zizhao Cheng ,&nbsp;Shengyao Wang ,&nbsp;Xuesi Hua ,&nbsp;Li Zhang ,&nbsp;Boya Li ,&nbsp;Huiling Li ,&nbsp;Yunya Bai ,&nbsp;Yali Li ,&nbsp;Jinping Hao ,&nbsp;Jianxiong Wang ,&nbsp;Lingyi Zhao ,&nbsp;Dan Gao ,&nbsp;Lan Zhang","doi":"10.1016/j.jpba.2025.116818","DOIUrl":"10.1016/j.jpba.2025.116818","url":null,"abstract":"<div><div>Given the growing incidence of dementia-related disorders in the aging population, identifying effective treatments for age-related cognitive decline (ARCD) is crucial. Shenwu Capsule (SWC), shown to have therapeutic efficacy in phase III clinical trials for senile dementia, has unclear mechanisms and active ingredients. Aged mice were administered SWC orally for three months, and behavioral tests, including the Morris water maze, Y maze, and novel object recognition, assessed learning and memory. Neuronal damage was evaluated using histopathology, and the levels of Aβ and phosphorylated tau proteins were measured. UPLC-Q-TOF-MS identified 11 components of SWC capable of crossing the blood-brain barrier (BBB), and network pharmacology was employed to explore their potential mechanisms. Through various detection methods, including transmission electron microscopy, Western blotting, qRT-PCR, ELISA, and immunofluorescence, six key targets (AKT1, TNF, TP53, SRC, EGFR, BCL2) were elucidated. GO and KEGG pathway analyses revealed that the PI3K/Akt signaling pathway plays a crucial role in the pharmacological effects of SWC. SWC was found to suppress neuronal apoptosis by activating the PI3K/Akt/Bcl-2 signaling pathway, as demonstrated by changes in mRNA and protein levels. Histological analysis further showed that SWC treatment restored mitochondrial morphology in the hippocampus of aged mice. Molecular docking simulations confirmed strong binding affinities between the active components and key targets. Psoralidin, a component with strong molecular docking potential, was shown in vitro to activate the PI3K/Akt/Bcl-2 pathway, reduce ROS, decrease apoptosis, improve mitochondrial morphology, and stabilize mitochondrial membrane potential. These protective effects were blocked by the PI3K inhibitor LY294002. Overall, SWC ameliorates ARCD through modulation of the PI3K/Akt/Bcl-2 signaling pathway, with psoralidin identified as a potential active ingredient.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"260 ","pages":"Article 116818"},"PeriodicalIF":3.1,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143674004","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}

{"title":"Impact of ultralow oxygen preservation on the quality of Atractylodis Macrocephalae Rhizoma evaluated by multi-chromatographic determination of small molecules and polysaccharides","authors":"Yu-Qing Zhu ,&nbsp;Jing-Wen Liu ,&nbsp;Jing Zhou ,&nbsp;Cheng-Ying Wu ,&nbsp;Fang Long ,&nbsp;Jin-Di Xu ,&nbsp;Shan-Shan Zhou ,&nbsp;Qian Mao ,&nbsp;Ming Kong ,&nbsp;Song-Lin Li ,&nbsp;Hong Shen","doi":"10.1016/j.jpba.2025.116813","DOIUrl":"10.1016/j.jpba.2025.116813","url":null,"abstract":"<div><div>Atractylodis Macrocephalae Rhizoma (AMR) is one of the commonly used medicinal and edible herbs in China. To prevent infestation of moths and mildew, chemical-fumigation is applied during post-harvest processing, which would produce harmful substances. Ultralow oxygen (ULO) storage, as a potential controlled atmosphere preservation method for Traditional Chinese Medicines (TCMs), has no residue of chemical hazards, but its impact on chemical composition of TCMs is unclear. Here, to evaluate the impact of ULO preservation on the quality of AMR, a UPLC-QTOF-MS/MS-based non-targeted metabolomics approach was employed to screen out the differential components after AMR had been stored under ULO conditions for 18 months. The differential components were identified, and further semi-quantified with peak areas. Additionally, the differential components with known activity were quantified using HPLC-DAD and GC-TQ-MS/MS analysis. The molecular weight distribution and monosaccharide composition of polysaccharides were analyzed using HPGPC-ELSD and HPLC-DAD to assess the impact of ULO on the carbohydrates. As it showed, 20 differential components of AMR under ULO were screened and identified when compared to normal atmosphere (NA) with 21 % oxygen concentration. As storage duration increased, the levels of atractylenolides I, II, and III in both ULO and NA storage conditions increased, with significant differences in their total content (16.06 mg/g in ULO vs. 47.57 mg/g in NA). Confirmatory experiments revealed that atractylone is the precursor compound of atractylenolides and the total content of atractylenolides I, II, and III produced from atractylone in ULO storage was only 62.12 % of that in NA at 18th month. The total sugar content of AMR polysaccharides in ULO storage was 107.28 % of that in NA and the molar ratios of monosaccharides were also relatively constant. All the results indicated that ULO preservation slowed down the chemical transformation of AMR, including small molecules and polysaccharides. Therefore, the quality of AMR stored in ULO is more stable and it is proposed to be an efficient preservation method for AMR.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"260 ","pages":"Article 116813"},"PeriodicalIF":3.1,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143620191","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}

{"title":"Reverse traceability analysis of estrogenic active ingredients in Cuscutae semen based on intestinal and hepatic metabolism","authors":"Xiangming Sun ,&nbsp;Mingyao Zhao ,&nbsp;Wei Liang ,&nbsp;Hui Song ,&nbsp;Zhongyuan Qu ,&nbsp;Liyang Sui ,&nbsp;Wenlan Li","doi":"10.1016/j.jpba.2025.116819","DOIUrl":"10.1016/j.jpba.2025.116819","url":null,"abstract":"<div><div>As a traditional Chinese medicine for reinforcing kidney, Cuscutae semen can be applied in regulating the level of estrogen. And nine direct-acting substances <em>in vivo</em> with estrogenic effect has been figured out according to our previous research. However, their transformation relationship and the prototype forms of some metabolites are still not clear, impeding the elucidation of the effective substances of Cuscutae semen. In this study, to reveal the metabolic pathways of nine direct-acting substances <em>in vivo</em>, the hepatic and intestinal metabolism of nine monomer components from Cuscutae semen were investigated using liver microsomes of female rats and intestinal flora in ovariectomized rats. Based on ultra performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC/Q-TOFMS) method, a total of 35 hepatic metabolites and three intestinal metabolites were tentatively identified respectively. The proposed metabolic pathways of main metabolites were discussed. Glucuronidation binding reactions played a dominant role in the hepatic metabolism. While in the intestinal metabolism, flavonoid glycosides were hydrolyzed into the aglycones without further phase II metabolic reaction. According to the achievements above, a reverse traceability analysis of the direct-acting substances <em>in vivo</em> was conducted, and the metabolic transformation relationship between the components was clarified except for methylated quercetin glucuronide. It is tentatively speculated that kaempferol, quercetin, apigenin, hyperin, astragalin and isoquercitrin in Cuscutae semen are potential estrogenic effective substances, which can be used as reference for quality control.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"260 ","pages":"Article 116819"},"PeriodicalIF":3.1,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143627841","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}

{"title":"The cutting edge of surveillance: Exploring high-resolution mass spectrometry in wastewater-based epidemiology for monitoring forensic samples","authors":"Asmaa Kamal El-Deen ,&nbsp;Chaudhery Mustansar Hussain","doi":"10.1016/j.jpba.2025.116821","DOIUrl":"10.1016/j.jpba.2025.116821","url":null,"abstract":"<div><div>Criminal activity has always been detected through forensic evidence. However, the potential for using such evidence to stop crimes in their tracks or slow them down has not yet been completely realized. There is a lot of potential for assessing trace quantities of chemicals in wastewater systems to provide effective forensic information. Wastewater-based epidemiology (WBE) has emerged in the last decades as a crucial epidemiological information source for collecting data on community-wide health. It can add important knowledge about illicit drug consumption and/or disposal, exposure to pathogens, infectious diseases, industrial pollutants, and antibiotic resistance. The use of high-resolution mass spectrometry (HRMS) in WBE has revolutionized the field by enabling the detection and quantification of these compounds. This review article explores the cutting edge of surveillance in WBE through applying HRMS techniques for forensic sample monitoring. It delves into the most recent WBE applications, examining their advantages and disadvantages. It also explores the potential for obtaining a more comprehensive evaluation of forensic samples. Furthermore, the application of these approaches to generate “forensic intelligence” for surveillance and criminal interruption is discussed, with examples of how this data can be integrated into future work.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"260 ","pages":"Article 116821"},"PeriodicalIF":3.1,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143601449","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}

{"title":"Utilizing copper-doped graphene quantum dots as a fluorescent sensor for determination of carbamazepine in exhaled breath condensate","authors":"Aylar Keyvani ,&nbsp;Vahid Jouyban-Gharamaleki ,&nbsp;Maryam Khoubnasabjafari ,&nbsp;Jafar Soleymani ,&nbsp;Elaheh Rahimpour ,&nbsp;Abolghasem Jouyban","doi":"10.1016/j.jpba.2025.116815","DOIUrl":"10.1016/j.jpba.2025.116815","url":null,"abstract":"<div><div>Carbamazepine is a versatile pharmaceutical used mainly for epilepsy and mood stabilization, but like all medications, it requires careful monitoring due to its potential side effects and interactions. In the current work, a fluorescent nanosensor was developed for the carbamazepine determination in the exhaled breath condensate (EBC). The nanosensor consists of graphene quantum dots doped with copper (Cu-doped GQDs). The presence of carbamazepine significantly decreased the fluorescence of Cu-doped GQDs, resulting in a quenching effect within a concentration range of 0.02–2.0 µg/mL, which occurs due to dynamic, rather than static, quenching according to Stern–Volmer plot. The relative standard deviations for intra-day and inter-day analysis of carbamazepine were 1.8 % and 4.8 %, respectively. The validated sensor was effectively employed for carbamazepine analysis in EBC of patients receiving the drug.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"260 ","pages":"Article 116815"},"PeriodicalIF":3.1,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143601451","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}

{"title":"Quantitative method for intestinal short chain fatty acids based on stable isotope labeling combined with liquid chromatography-mass spectrometry","authors":"Yang Zhang ,&nbsp;Yan Qiao ,&nbsp;Xin Ding ,&nbsp;Ya Zhang ,&nbsp;Xuemei Su ,&nbsp;Lei Zhang ,&nbsp;Qian Zhou ,&nbsp;Guangguo Tan","doi":"10.1016/j.jpba.2025.116798","DOIUrl":"10.1016/j.jpba.2025.116798","url":null,"abstract":"<div><div>Short chain fatty acids (SCFAs) are produced from the breakdown of dietary proteins and fiber by gut microbes, and they have a close relationship with the health and diseases of the host. However, due to the similar structures of SCFAs, the abundance of active molecules, the wide concentration range in biological samples, and the characteristics such as high polarity, poor chromatographic separation, and ionization performance, it is challenging to comprehensively and accurately quantify SCFAs. This study utilized a stable isotope-labeled carboxyl derivatization reagent <em>d</em>_<em>0</em><em>-/d</em>_<em>6</em>-2,4-dimethoxy-6-piperazin-1-yl pyrimidine (<em>d</em>_<em>0</em><em>-/d</em>_<em>6</em>-DMPP) to establish a new method for the wide-coverage quantification analysis of SCFAs using ultra-high performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UHPLC-ESI-MS/MS), capable of detecting the content of 16 SCFAs. The method demonstrated low limits of detection (LODs) of 0.05–0.5 nmol/L and limits of quantification (LOQs) of 0.1–1.0 nmol/L, with excellent linearity (R² &gt; 0.99), intra-day precision (RSD &lt; 8.5 %), and inter-day precision (RSD &lt; 7.8 %). Using this quantitative analysis method, we successfully quantified 16 SCFAs from the colonic contents of rats with 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced ulcerative colitis (UC) and Sini decoction (SND) intervention. It was found that after the interventional treatment with SND, the levels of 7 SCFAs in the colonic contents of rats with UC were significantly up regulated, including acetic acid, propionic acid, butyric acid, isobutyric acid, valeric acid, 2-methylbutyric acid, and hexanoic acid, while 4 SCFAs were significantly down regulated, including 3-hydroxyisovaleric, 3-methyl-2-oxobutanoic acid, 3-methyl-2-oxovaleric acid, and 4-methyl-2-oxovaleric acid. These findings suggested that SND might exert its therapeutic effect on UC by regulating the metabolism of SCFAs. Overall, this study not only provides a new method for the analysis of SCFAs with high sensitivity and wide-coverage but also offers important scientific evidence for understanding the mechanism of SND against UC.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"260 ","pages":"Article 116798"},"PeriodicalIF":3.1,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143611319","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}

{"title":"GC and HPLC-RID method development and validation for the determination of twelve related substances, including several novel compounds in tetrabenazine","authors":"Dong-shuo Meng ,&nbsp;Guo-jing Li ,&nbsp;Shen-guo Sun ,&nbsp;Chun-xin Ma ,&nbsp;Tian-quan Zhu ,&nbsp;Yu Liu","doi":"10.1016/j.jpba.2025.116814","DOIUrl":"10.1016/j.jpba.2025.116814","url":null,"abstract":"<div><div>A series of GC-FID and HPLC-RID methods were developed and rigorously validated for the detection of various aldehyde and ketone impurities, including 5-methyl-2-hexanone and 5-methyl-3-hexen-2-one, as well as quaternary ammonium salt impurity that lack UV absorption, during the synthesis of tetrabenazine. Six novel compounds, three have not been previously reported, were synthesized and their structures confirmed. This was achieved through a comprehensive investigation into impurity transmission chains and their clearance throughout the synthesis process. The limits for all detected impurities, which included a total of twelve related substances, were established at approximately 0.1 %. The LOD for the developed analytical methods ranged from 0.3 μg mL⁻¹ to 12.5 μg mL⁻¹.</div></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":"260 ","pages":"Article 116814"},"PeriodicalIF":3.1,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143601450","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}