Journal of Pharmaceutical and Biomedical Analysis Open最新文献

Magnetic solid-phase extraction of Sudan dyes from beverages-coated magnetite/silica materials

Journal of Pharmaceutical and Biomedical Analysis Open Pub Date : 2025-03-12 DOI: 10.1016/j.jpbao.2025.100073

Yugao Guo , Xiaoxiao Niu , Boyu Li , Pei Liu , Youqing Sun , Sumin Lu

{"title":"Magnetic solid-phase extraction of Sudan dyes from beverages-coated magnetite/silica materials","authors":"Yugao Guo , Xiaoxiao Niu , Boyu Li , Pei Liu , Youqing Sun , Sumin Lu","doi":"10.1016/j.jpbao.2025.100073","DOIUrl":"10.1016/j.jpbao.2025.100073","url":null,"abstract":"<div><div>In this study, a polydopamine-coated magnetite/silica composite material (Fe<sub>3</sub>O<sub>4</sub>@SiO<sub>2</sub>/PDA) was successfully synthesized and characterized using Fourier-transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS). By integrating EM-MSPE with high-performance liquid chromatography (HPLC), a novel EM-MSPE-HPLC method was established for the sensitive and accurate determination of Sudan I-IV dyes. Key experimental parameters, such as adsorbent dosage, pH, inorganic salt concentration, adsorption time, voltage, eluent type, eluent volume, and desorption time, were systematically investigated and optimized. Under optimal conditions, the method demonstrated excellent linearity (R² > 0.999) within a concentration range of 5–1000 μg L⁻¹, with limits of detection (LODs) ranging from 0.11 to 0.17 μg L⁻¹. The recoveries of Sudan dyes in real samples ranged from 89.1 % to 101.9 %, with relative standard deviations (RSDs) between 0.3 % and 3.6 %. Furthermore, the Fe<sub>3</sub>O<sub>4</sub>@SiO<sub>2</sub>/PDA adsorbent exhibited consistent performance over ten consecutive extraction cycles without significant loss in recovery efficiency. These findings demonstrate that the proposed method is accurate, reliable, and reproducible for the simultaneous determination of Sudan dyes in complex beverage matrices, offering a robust analytical approach for food safety applications.</div></div>","PeriodicalId":100822,"journal":{"name":"Journal of Pharmaceutical and Biomedical Analysis Open","volume":"5 ","pages":"Article 100073"},"PeriodicalIF":0.0,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143686909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Direct sample introduction in high-performance liquid chromatography analysis of oily medicinal cannabis samples using surfactant-free microemulsion

Journal of Pharmaceutical and Biomedical Analysis Open Pub Date : 2025-03-11 DOI: 10.1016/j.jpbao.2025.100075

Ana Paula Lamounier, Bárbara da Conceição Coelho Cotta Cardoso, Alessandra Licursi Maia Cerqueira da Cunha

{"title":"Direct sample introduction in high-performance liquid chromatography analysis of oily medicinal cannabis samples using surfactant-free microemulsion","authors":"Ana Paula Lamounier, Bárbara da Conceição Coelho Cotta Cardoso, Alessandra Licursi Maia Cerqueira da Cunha","doi":"10.1016/j.jpbao.2025.100075","DOIUrl":"10.1016/j.jpbao.2025.100075","url":null,"abstract":"<div><div>The therapeutic use of medicinal Cannabis has raised challenges in quality control and cannabinoid quantification in oil extracts, primarily due to incompatibility with liquid chromatography systems. Surfactant-free microemulsion (SFME) systems offer a promising, efficient, and sustainable solution, enabling direct analysis by high-performance liquid chromatography. These microemulsions are dispersions of two immiscible liquids, typically oil and water, made compatible by an amphiphilic substance that interacts with both polar and nonpolar fractions. After SFME testing and critical analysis of the results, clear and homogeneous microemulsions were observed regardless of the oil-to-water ratio studied, provided that sufficient quantities of 1-octanol:1-propanol (3:10 v/v) were added. Based on the established robust working range, the 1:2 (oil:ultrapure water) ratio (% w/w) was chosen as the compromise condition, minimizing medicinal oil use while ensuring compatibility with the chromatographic system. Univariate optimization of chromatographic conditions enabled simultaneous analysis of five cannabinoids, including cannabidiol (CBD), cannabidiolic acid (CBDA), tetrahydrocannabutol (THCB), cannabinol (CBN), and tetrahydrocannabinol (Δ9-THC) using a ZORBAX Eclipse Plus C18 column at 35 °C. The method employed isocratic elution with a mobile phase of 82:18 %v/v methanol:ultrapure water containing 0.15 ± 0.05 % v/v formic acid, a 1.0 mL min<sup>−1</sup> flow rate, and a 20 μL injection volume, using the fluorescence and UV absorption detectors. This proposal offers sensitivity (LOD in the ng mL<sup>−1</sup>), selectivity, and separation efficiency, associated with low cost, minimal waste generation, and low energy demand, aligning with Green Chemistry principles.</div></div>","PeriodicalId":100822,"journal":{"name":"Journal of Pharmaceutical and Biomedical Analysis Open","volume":"5 ","pages":"Article 100075"},"PeriodicalIF":0.0,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143644376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Interstitial fluid-based optical biosensors

Journal of Pharmaceutical and Biomedical Analysis Open Pub Date : 2025-03-10 DOI: 10.1016/j.jpbao.2025.100074

Atefeh Rahimzadeh , Abrisham Arjomandkhah , Mohammad Ali Kiani, Hamed Golmohammadi

引用次数: 0

How does HSA's antioxidant activity change under the influence of lincomycin and spectinomycin mixture? – A spectroscopic study

Journal of Pharmaceutical and Biomedical Analysis Open Pub Date : 2025-03-08 DOI: 10.1016/j.jpbao.2025.100070

Wojciech Rogóż, Aleksandra Owczarzy, Karolina Kulig, Małgorzata Maciążek-Jurczyk

{"title":"How does HSA's antioxidant activity change under the influence of lincomycin and spectinomycin mixture? – A spectroscopic study","authors":"Wojciech Rogóż, Aleksandra Owczarzy, Karolina Kulig, Małgorzata Maciążek-Jurczyk","doi":"10.1016/j.jpbao.2025.100070","DOIUrl":"10.1016/j.jpbao.2025.100070","url":null,"abstract":"<div><div>Lincomycin (LIN) belongs to the lincosamides group and is used in bacterial infections of soft tissues, the respiratory system, bone marrow, and bones, while spectinomycin (SPE) belongs to the group of aminoglycoside antibiotics and is used for the treatment of gonorrhoea. Both antibiotics are commonly used to treat humans separately while their mixture is used in veterinary preparations (SPE-LIN), and the combination of these antibiotics has not yet been used for human treatment. The aim of this study was to search for modulators of human serum albumin (HSA) antioxidant activity among antibacterial drugs, lincomycin (LIN) and spectinomycin (SPE). In order to study the effect of LIN and SPE on HSA antioxidant properties the DPPH and ABTS tests were used. UV-Vis spectrophotometry and circular dichroism (CD) spectroscopic techniques were used to find the cause of LIN and SPE modulatory activity related to HSA antiradical potential. Both LIN and SPE, as well as their mixture, did not show significant antioxidant activity, while in combination with HSA, they stimulated its antioxidant properties. CD measurements determined that the dominant secondary structure of HSA, regardless of the presence of ligands, was α-helix, and its percentage share slightly increased under the influence of LIN and SPE. The obtained results confirm the viability of further studies on the potential application of the combination of SPE-LIN in the treatment, not only in breeding animals. The proposed concept of research may be a response to the future needs in medicine. The assumed goal, which was the search for HSA modulators, has been achieved.</div></div>","PeriodicalId":100822,"journal":{"name":"Journal of Pharmaceutical and Biomedical Analysis Open","volume":"5 ","pages":"Article 100070"},"PeriodicalIF":0.0,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143601102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

“Quartz crystal microbalance-based biosensor for rapid and ultrasensitive SARS-CoV-2 detection"

Journal of Pharmaceutical and Biomedical Analysis Open Pub Date : 2025-03-07 DOI: 10.1016/j.jpbao.2025.100071

Sahera Saleh , Habib Alkalamouni , Karen Antar , Joe Rahme , Michel Kazan , Pierre Karam , Jit Muthuswamy , Hassan Zaraket , Massoud L. Khraiche

{"title":"“Quartz crystal microbalance-based biosensor for rapid and ultrasensitive SARS-CoV-2 detection\"","authors":"Sahera Saleh , Habib Alkalamouni , Karen Antar , Joe Rahme , Michel Kazan , Pierre Karam , Jit Muthuswamy , Hassan Zaraket , Massoud L. Khraiche","doi":"10.1016/j.jpbao.2025.100071","DOIUrl":"10.1016/j.jpbao.2025.100071","url":null,"abstract":"<div><div>The COVID-19 pandemic highlighted the urgent need for rapid, sensitive, and affordable diagnostic tests, especially in resource-limited settings. While RT-qPCR remains the gold standard for SARS-CoV-2 detection, it is expensive and requires specialized equipment. Antigen-based tests, though faster, lack sufficient sensitivity. Therefore, there is a pressing need for a platform that combines the rapidity of antigen tests with the sensitivity of molecular tests. In this work, we address this problem by developing a Quartz Crystal Microbalance (QCM) biosensor for the rapid detection of SARS-CoV-2 nucleocapsid proteins. We designed a QCM biosensor with polyethylene glycol (PEG)-based surface functionalization, which significantly improves sensitivity and specificity. The platform achieved a detection limit of 53.3 TCID<sub>50</sub>/mL and a sensitivity of 0.263 Hz/ TCID<sub>50</sub>/mL, with results available in approximately 15 min. Cross-reactivity tests with Influenza A demonstrated its high specificity for SARS-CoV-2. Comprehensive surface characterization using Scanning Electron Microscopy (SEM), Digital Holographic Microscopy, and Raman Spectroscopy confirmed the stability and integrity of the functionalized sensor surface. The platform is cost-effective, scalable, and designed for ease of use in resource-limited settings. This work presents the first open-source QCM biosensing platform for SARS-CoV-2 detection that combines high sensitivity, rapid results, and affordability. It offers a deployable solution for COVID-19 diagnostics, particularly in underserved regions, and is adaptable for future pandemic preparedness.</div></div>","PeriodicalId":100822,"journal":{"name":"Journal of Pharmaceutical and Biomedical Analysis Open","volume":"5 ","pages":"Article 100071"},"PeriodicalIF":0.0,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143686908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Therapeutic siRNA quantification in lipid nanoparticles using ion-pair reversed-phase chromatography

Journal of Pharmaceutical and Biomedical Analysis Open Pub Date : 2025-03-03 DOI: 10.1016/j.jpbao.2025.100072

Ludivine Ferey, Sandy Al Bardawil, Emilie Dols, Aurore Guédin, Viet-Ha Phan, Philippe Barthélémy, Jeanne Leblond Chain

{"title":"Therapeutic siRNA quantification in lipid nanoparticles using ion-pair reversed-phase chromatography","authors":"Ludivine Ferey, Sandy Al Bardawil, Emilie Dols, Aurore Guédin, Viet-Ha Phan, Philippe Barthélémy, Jeanne Leblond Chain","doi":"10.1016/j.jpbao.2025.100072","DOIUrl":"10.1016/j.jpbao.2025.100072","url":null,"abstract":"<div><div>The clinical development of lipid nanoparticles encapsulating small interfering RNA (siRNA-LNP) requires robust and efficient analytical methods for quality assessment. In this study, we investigated the chromatographic profiles of siRNAs using Ion-Pair Reversed-Phase (IP-RP) HPLC at six different temperatures, including the melting temperature of duplexes, on two RP columns. The column temperature was identified as a critical parameter influencing chromatographic profiles, with characteristic profiles evolving in a temperature-dependent manner, corresponding to the melting temperatures (T<sub>m</sub>) of the two siRNA duplexes analyzed, across both tested columns. Moreover, the siRNA dissociation observed on the columns was consistent with the melting temperatures of the duplexes measured by UV-Vis spectroscopy under HPLC mobile phase conditions. An IP-RPHPLC method using 100 mM TEAA with ACN and a column temperature of 80 °C, above the T<sub>m</sub> of the analyzed duplexes, was successfully applied for the quantitative determination of siRNAs in LNP formulations. A simple, one-step sample preparation was employed by directly adding a neutral surfactant to the LNP samples before injection. This method proved highly accurate, as shown by a 100 % recovery of siRNA immediately following microfluidic formulation. Additionally, the impact of the dialysis purification process on siRNA recovery was assessed, revealing a 30 % loss of siRNA. Importantly, the results obtained from this method were consistent with those from the fluorescence reference method. This method helps improve the quality control of siRNA-LNP therapeutics, thereby enhancing their clinical translation potential and supporting the development of next-generation RNA-based therapies.</div></div>","PeriodicalId":100822,"journal":{"name":"Journal of Pharmaceutical and Biomedical Analysis Open","volume":"5 ","pages":"Article 100072"},"PeriodicalIF":0.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143593207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Laser-induced graphene electrodes obtained by direct laser writing for pharmaceutical and biomedical analysis

Journal of Pharmaceutical and Biomedical Analysis Open Pub Date : 2025-03-01 DOI: 10.1016/j.jpbao.2025.100069

Amal Rabti , Sabrine Baachaoui , Mohamed Zouari , Noureddine Raouafi

{"title":"Laser-induced graphene electrodes obtained by direct laser writing for pharmaceutical and biomedical analysis","authors":"Amal Rabti , Sabrine Baachaoui , Mohamed Zouari , Noureddine Raouafi","doi":"10.1016/j.jpbao.2025.100069","DOIUrl":"10.1016/j.jpbao.2025.100069","url":null,"abstract":"<div><div>Laser-induced graphene (LIG), also referred to as laser-ablated graphene (LAG), laser-scribed graphene (LSG), laser-produced graphene (LPG), laser-engineered graphene (LEG), and laser-derived graphene (LDG), has emerged as a versatile material for the development of high-performance electrodes that exhibit unique properties, such as high electrical conductivity, large surface area, chemical stability, and ease of functionalization. These characteristics render LIG electrodes particularly suitable for pharmaceutical and biomedical applications where rapid, sensitive, and reliable analytical methods are required. This review presents a comprehensive overview of recent advancements in the utilization of graphene electrodes for pharmaceutical and biomedical applications. They encompass their fabrication processes, surface modifications with nanomaterials and biomolecules, and the principal analytical techniques employed, including electrochemical sensing, biosensing, and drug monitoring. Particular emphasis is placed on the integration of LIG electrodes into point-of-care devices for clinical diagnostics and therapeutic drug monitoring, as well as their role in detecting biomarkers and pharmaceutical residues. Furthermore, the challenges and future perspectives for LIG electrodes in achieving widespread adoption in the biomedical and pharmaceutical fields are examined, underscoring the need for improved scalability, selectivity, and regulatory compliance. This review elucidates the transformative potential of LIG-based technologies for addressing emerging healthcare challenges through innovative and cost-effective analytical solutions.</div></div>","PeriodicalId":100822,"journal":{"name":"Journal of Pharmaceutical and Biomedical Analysis Open","volume":"5 ","pages":"Article 100069"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143548765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A novel microextraction method for further elemental impurity determination in oily pharmaceutical excipients by ICP-MS

Journal of Pharmaceutical and Biomedical Analysis Open Pub Date : 2025-03-01 DOI: 10.1016/j.jpbao.2025.100063

Cristian Rafael Andriolli , Mariele Samuel Nascimento , Alessandra Schneider Henn , Eder Lisandro Moraes Flores , Erico Marlon Moraes Flores , Rochele Sogari Picoloto

{"title":"A novel microextraction method for further elemental impurity determination in oily pharmaceutical excipients by ICP-MS","authors":"Cristian Rafael Andriolli , Mariele Samuel Nascimento , Alessandra Schneider Henn , Eder Lisandro Moraes Flores , Erico Marlon Moraes Flores , Rochele Sogari Picoloto","doi":"10.1016/j.jpbao.2025.100063","DOIUrl":"10.1016/j.jpbao.2025.100063","url":null,"abstract":"<div><div>In this study, a reversed-phase dispersive liquid-liquid microextraction (RP-DLLME) method was proposed for the subsequent determination of elemental impurities of class 1 (As, Cd, Hg, and Pb) and class 2 A (Co, Ni, and V) in oily pharmaceutical excipients, as recommended by the International Council for Harmonisation (ICH) guideline Q3D. Analyte determination was carried out by inductively coupled plasma mass spectrometry (ICP-MS). Operational parameters were evaluated, including dispersant and extractant solvents, total volume and proportion of the extraction solution, sample mass, temperature, heating time, centrifugation, and stirring. Suitable results were obtained using a high sample mass (5 g), 2 mL of 50:50 % (v/v) of <em>n</em>-propanol:HNO<sub>3</sub> (3 mol L<sup>−1</sup> HNO<sub>3</sub> for all analytes and 6 mol L<sup>−1</sup> HCl only for Hg), heating at 85 °C for 20 min, stirring for 1 min, and centrifugation for 10 min. Accuracy was assessed using certified reference materials (CRMs) of mineral oil, comparison with a reference method (microwave-assisted wet digestion), and analyte recovery experiments at three concentration levels, following ICH Q3D recommendations and the United States Pharmacopeia (USP) guidelines for injectable drugs. No statistical differences were observed in any of the accuracy assessments. The method achieved low quantification limits (LOQs) of 0.045, 0.006, 0.006, 0.009, 0.040, 0.020, and 0.102 µg g<sup>−1</sup> for As, Cd, Co, Hg, Ni, Pb, and V, respectively, all of which were below the maximum levels allowed by the ICH guideline. The proposed method presented several advantages for routine analysis, including simplicity, high throughput, the use of diluted solutions, and minimal laboratory waste generation.</div></div>","PeriodicalId":100822,"journal":{"name":"Journal of Pharmaceutical and Biomedical Analysis Open","volume":"5 ","pages":"Article 100063"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143576883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Turning diverse analytical data into actionable knowledge for enzymatically driven polysorbate degradation risk assessment and control in biotherapeutic protein formulations

Journal of Pharmaceutical and Biomedical Analysis Open Pub Date : 2025-02-24 DOI: 10.1016/j.jpbao.2025.100068

Alex Dow , Divya Chandra , Ximeng Dow , Benjamin Adams , Morgan Ayres , Shannon Rivera , Rong-Sheng Yang , Anita P. Liu , Xuanwen Li , Tingting Jiang , Fengqiang Wang , Tony Pereira , Rosalind Ang , Chunyan Li , Lei Zhang , Jonathan Welch , Lloyd Breunig

{"title":"Turning diverse analytical data into actionable knowledge for enzymatically driven polysorbate degradation risk assessment and control in biotherapeutic protein formulations","authors":"Alex Dow , Divya Chandra , Ximeng Dow , Benjamin Adams , Morgan Ayres , Shannon Rivera , Rong-Sheng Yang , Anita P. Liu , Xuanwen Li , Tingting Jiang , Fengqiang Wang , Tony Pereira , Rosalind Ang , Chunyan Li , Lei Zhang , Jonathan Welch , Lloyd Breunig","doi":"10.1016/j.jpbao.2025.100068","DOIUrl":"10.1016/j.jpbao.2025.100068","url":null,"abstract":"<div><div>In recent years polysorbate (PS) degradation in biotherapeutic protein formulations has become one of the most challenging topics for residual host cell protein control. With such focus, various assays have been showcased to help inform on enzymatically driven PS degradation risk assessment and control. Access to multiple, orthogonal data sets can improve understanding but also increases complexity in data interpretation. To highlight how multiple assays can work together to provide an aligned enzymatically driven PS degradation risk assessment and control, three cases studies are discussed. The case studies are diverse in the driver for performing these experiments along with if they are proactively or reactively addressing PS degradation. From these three case studies it becomes apparent that assays are consistent in their use and alignment regarding enzymatically driven PS degradation risk assessment and control. In general, an assay will fall into one of three categories: risk informing, characterization, and extended characterization. With this information future work focused on enzymatically driven PS degradation risk assessment and control has a blueprint for what assays can be used and what the data informs on.</div></div>","PeriodicalId":100822,"journal":{"name":"Journal of Pharmaceutical and Biomedical Analysis Open","volume":"5 ","pages":"Article 100068"},"PeriodicalIF":0.0,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143644374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Innovative QSRR modeling approach for the development of an ultra-sensitive LC-MS/MS method for trace analysis of N-nitrosamines

Journal of Pharmaceutical and Biomedical Analysis Open Pub Date : 2025-02-19 DOI: 10.1016/j.jpbao.2025.100064

Yue Zhang, Sabah Houari, Thomas Van Laethem, Amandine Dispas, Eric Ziemons, Philippe Hubert, Cédric Hubert

{"title":"Innovative QSRR modeling approach for the development of an ultra-sensitive LC-MS/MS method for trace analysis of N-nitrosamines","authors":"Yue Zhang, Sabah Houari, Thomas Van Laethem, Amandine Dispas, Eric Ziemons, Philippe Hubert, Cédric Hubert","doi":"10.1016/j.jpbao.2025.100064","DOIUrl":"10.1016/j.jpbao.2025.100064","url":null,"abstract":"<div><div>To address regulatory concerns regarding N-nitrosamine contamination in pharmaceutical products, generic LC-MS/MS methods for determining N-nitrosamines were developed using an innovative <em>in silico</em> approach based on Quantitative Structure Retention Relationship modeling (QSRR). The development process included screening and optimization phases, offering flexibility in targeting N-nitrosamines and addressing the challenges related to the matrix effect. This methodology represents a significant advancement in method development. Among the developed methods, a highly sensitive and accurate LC-MS/MS method was successfully validated to simultaneously determine 5 small-molecule N-nitrosamine impurities in tablets, which was used in the present proof-of-concept study. The validation followed the ICH Q2 (R2) guidelines, employing a combined approach for accuracy and precision based on total error risk-based methodology. The method was validated to function as both an impurity limit test and a quantitative method. Validation results demonstrated adequate quantitative performance of the method, establishing a validated dosing range from 1 to 30 ng/mL for all N-nitrosamines. The estimated detection limit ranged from 0.75 pg/mL to 0.02 ng/mL. The detection and quantification limits for each N-nitrosamine met the EMA N-nitrosamine investigation approach requirements. Moreover, both are always below 10 % of their respective acceptable limit in the studied finished product formulation. This proposed method is suitable for investigating small-molecule N-nitrosamines in pharmaceutical products and also provides a starting point for further method development, particularly for the determination of newly identified small-molecule N-nitrosamines and drug-substance-related N-nitrosamines.</div></div>","PeriodicalId":100822,"journal":{"name":"Journal of Pharmaceutical and Biomedical Analysis Open","volume":"5 ","pages":"Article 100064"},"PeriodicalIF":0.0,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143445617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0