Pub Date : 2025-09-20DOI: 10.1016/j.jpbao.2025.100091
Abdullah Al Faysal, Beril S. Kaya, Hatice Elmacioglu, Ayşegül Gölcü
Turkey has historically been a prominent player in the trade of medicinal and aromatic plants, a status attributed to its advantageous geographical position, favorable climate, rich plant diversity, agricultural capabilities, and extensive land area. The country's flora is home to numerous species that are integral to established practices in herbal medicine, as well as the global manufacturing of plant-based chemicals, food additives, cosmetics, and perfumery. Recent research has particularly emphasized the role of antioxidant substances and phenolic compounds found in plants in promoting health. This review thoroughly evaluates the analytical techniques utilized in assessing antioxidant activity, drawing attention to the essential chemical reactions that underpin these measurements. Furthermore, the article compellingly highlights the significant role of antioxidants across various industries, demonstrating their crucial contributions to health, food preservation, and beyond. Furthermore, an in-depth analysis of the antioxidant properties of Turkish plant extracts is presented, detailing their constituent components, the solvents utilized for extraction, and the methodologies applied in antioxidant research.
{"title":"A comprehensive evaluation of contemporary techniques employed to measure the antioxidant activity of plant extracts from Turkey, both in vitro and in vivo","authors":"Abdullah Al Faysal, Beril S. Kaya, Hatice Elmacioglu, Ayşegül Gölcü","doi":"10.1016/j.jpbao.2025.100091","DOIUrl":"10.1016/j.jpbao.2025.100091","url":null,"abstract":"<div><div>Turkey has historically been a prominent player in the trade of medicinal and aromatic plants, a status attributed to its advantageous geographical position, favorable climate, rich plant diversity, agricultural capabilities, and extensive land area. The country's flora is home to numerous species that are integral to established practices in herbal medicine, as well as the global manufacturing of plant-based chemicals, food additives, cosmetics, and perfumery. Recent research has particularly emphasized the role of antioxidant substances and phenolic compounds found in plants in promoting health. This review thoroughly evaluates the analytical techniques utilized in assessing antioxidant activity, drawing attention to the essential chemical reactions that underpin these measurements. Furthermore, the article compellingly highlights the significant role of antioxidants across various industries, demonstrating their crucial contributions to health, food preservation, and beyond. Furthermore, an in-depth analysis of the antioxidant properties of Turkish plant extracts is presented, detailing their constituent components, the solvents utilized for extraction, and the methodologies applied in antioxidant research.</div></div>","PeriodicalId":100822,"journal":{"name":"Journal of Pharmaceutical and Biomedical Analysis Open","volume":"6 ","pages":"Article 100091"},"PeriodicalIF":0.0,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145157521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-16DOI: 10.1016/j.jpbao.2025.100089
Erika Maria Ricci , Miryam Perrucci , Marcello Locatelli , Imran Ali , Halil I. Ulusoy , Abuzar Kabir , Fotouh R. Mansour
Growing concerns over environmental pollution have led to increased emphasis on Green Chemistry and, more specifically, Green Analytical Chemistry (GAC). These frameworks advocate for the reduction of hazardous substances, minimization of waste, and consideration of the entire life cycle of analytical procedures—from production to disposal. Within this context, miniaturized analytical techniques have emerged as sustainable and efficient alternatives to conventional methods. Among these, capillary liquid chromatography (cLC), nano-liquid chromatography (nano-LC), and various modes of capillary electrophoresis (CE)—including micellar electrokinetic chromatography (MEKC), capillary isotachophoresis (CITP), capillary zone electrophoresis (CZE), capillary isoelectric focusing (CIEF), and capillary gel electrophoresis (CGE) have gained significant traction. Their advantages in terms of reduced solvent and sample consumption, enhanced resolution, and faster analysis times have made them particularly valuable in pharmaceutical and biomedical applications. One critical application area is the chiral separation of active pharmaceutical ingredients (APIs), which is increasingly vital in biotechnology, chemistry, agriculture, and especially the pharmaceutical industry. Electrokinetic chromatography (EKC) has proven to be an effective and versatile technique for this purpose, offering high resolution, flexibility, speed, and cost-efficiency. The growing availability of novel chiral selectors further enhances its appeal for the separation of enantiomeric drug compounds. This review provides an overview of recent advancements in miniaturized analytical techniques and highlights their applications in the biomedical and pharmaceutical sectors, with a particular focus on chiral separations using EKC.
{"title":"Miniaturization in action: High-resolution, low-cost analytical platforms for biomedical and pharmaceutical research","authors":"Erika Maria Ricci , Miryam Perrucci , Marcello Locatelli , Imran Ali , Halil I. Ulusoy , Abuzar Kabir , Fotouh R. Mansour","doi":"10.1016/j.jpbao.2025.100089","DOIUrl":"10.1016/j.jpbao.2025.100089","url":null,"abstract":"<div><div>Growing concerns over environmental pollution have led to increased emphasis on Green Chemistry and, more specifically, Green Analytical Chemistry (GAC). These frameworks advocate for the reduction of hazardous substances, minimization of waste, and consideration of the entire life cycle of analytical procedures—from production to disposal. Within this context, miniaturized analytical techniques have emerged as sustainable and efficient alternatives to conventional methods. Among these, capillary liquid chromatography (cLC), nano-liquid chromatography (nano-LC), and various modes of capillary electrophoresis (CE)—including micellar electrokinetic chromatography (MEKC), capillary isotachophoresis (CITP), capillary zone electrophoresis (CZE), capillary isoelectric focusing (CIEF), and capillary gel electrophoresis (CGE) have gained significant traction. Their advantages in terms of reduced solvent and sample consumption, enhanced resolution, and faster analysis times have made them particularly valuable in pharmaceutical and biomedical applications. One critical application area is the chiral separation of active pharmaceutical ingredients (APIs), which is increasingly vital in biotechnology, chemistry, agriculture, and especially the pharmaceutical industry. Electrokinetic chromatography (EKC) has proven to be an effective and versatile technique for this purpose, offering high resolution, flexibility, speed, and cost-efficiency. The growing availability of novel chiral selectors further enhances its appeal for the separation of enantiomeric drug compounds. This review provides an overview of recent advancements in miniaturized analytical techniques and highlights their applications in the biomedical and pharmaceutical sectors, with a particular focus on chiral separations using EKC.</div></div>","PeriodicalId":100822,"journal":{"name":"Journal of Pharmaceutical and Biomedical Analysis Open","volume":"6 ","pages":"Article 100089"},"PeriodicalIF":0.0,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145104307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-15DOI: 10.1016/j.jpbao.2025.100090
Wenning Zhu , Xinyu Liu , Yaping Zhao , Jingwei Wang , Xuwen Zhang , Chenxi Liu
Albendazole (ABZ) exists as two solid-state isomers: the amino form (Form I) and the imino form (Form II). While Form II significantly influences bioavailability, current analytical methods primarily focus on qualitative identification of polymorphs or quantify only Form I in raw materials. To address the lack of quantitative methods for both isomers in formulations, we developed a novel near-infrared (NIR) spectroscopy–based approach. This work established a validated quantitative model. ABZ Form II was prepared and characterized via X–ray diffraction, thermal analysis, and Raman imaging. Commercial albendazole tablets were simulated by spiking Form II into excipients at gradient concentrations (5–95 % w/w). The near-infrared (NIR) spectra were screened with preprocessing methods and wavenumber regions. A Factor was set that included the comprehensive determination coefficient (R2), root mean square error of cross validation (RMSECV), Bias and relative percentage deviation (RPD). Models with a Factor score < 0.5 or recovery rates outside 90–110 % were excluded. The method demonstrated high precision (RSD = 0.07 %), with LOD and LOQ values of 0.7840 ± 0.0028 % w/w and 3.0243 ± 0.0139 % w/w, respectively. In summary, this is the first reported NIR method for simultaneous quantification of ABZ Form I and Form II in tablets, providing a rapid, non–destructive tool for pharmaceutical quality control
{"title":"Quantitative analysis of Form II in albendazole formulations using near-infrared spectroscopy and partial least squares analysis","authors":"Wenning Zhu , Xinyu Liu , Yaping Zhao , Jingwei Wang , Xuwen Zhang , Chenxi Liu","doi":"10.1016/j.jpbao.2025.100090","DOIUrl":"10.1016/j.jpbao.2025.100090","url":null,"abstract":"<div><div>Albendazole (ABZ) exists as two solid-state isomers: the amino form (Form I) and the imino form (Form II). While Form II significantly influences bioavailability, current analytical methods primarily focus on qualitative identification of polymorphs or quantify only Form I in raw materials. To address the lack of quantitative methods for both isomers in formulations, we developed a novel near-infrared (NIR) spectroscopy–based approach. This work established a validated quantitative model. ABZ Form II was prepared and characterized via X–ray diffraction, thermal analysis, and Raman imaging. Commercial albendazole tablets were simulated by spiking Form II into excipients at gradient concentrations (5–95 % w/w). The near-infrared (NIR) spectra were screened with preprocessing methods and wavenumber regions. A Factor was set that included the comprehensive determination coefficient (R<sup>2</sup>), root mean square error of cross validation (RMSECV), Bias and relative percentage deviation (RPD). Models with a Factor score < 0.5 or recovery rates outside 90–110 % were excluded. The method demonstrated high precision (RSD = 0.07 %), with LOD and LOQ values of 0.7840 ± 0.0028 % w/w and 3.0243 ± 0.0139 % w/w, respectively. In summary, this is the first reported NIR method for simultaneous quantification of ABZ Form I and Form II in tablets, providing a rapid, non–destructive tool for pharmaceutical quality control</div></div>","PeriodicalId":100822,"journal":{"name":"Journal of Pharmaceutical and Biomedical Analysis Open","volume":"6 ","pages":"Article 100090"},"PeriodicalIF":0.0,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145104304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Biosensors utilising nanotechnology are advancing swiftly and are extensively employed across various domains, including biomedicine, environmental monitoring, and analytical chemistry, where they have attained significant roles. Novel nanomaterials are being extensively designed and produced for prospective biosensing and theranostic uses. This review provides a comprehensive analysis of relevant literature from the past ten years, focusing on the use of nanoparticles in this context. The amalgamation of diagnostic biosensors with drug delivery systems for the administration of therapeutic agents presents significant potential in next-generation theranostic platforms. The controllable, precise, and safe delivery of diagnostic biosensing devices and therapeutic drugs to target tissues, organs, or cells is a crucial factor in the development of improved nanobiosensor-based theranostic systems. Recently, the utilisation of natural biological carriers in drug delivery systems has become one of the most extensively studied research issues. Erythrocytes, or red blood cells, may serve as carriers for a diverse array of pharmaceuticals, encompassing anticancer, antibacterial, antiviral, and anti-inflammatory agents, as well as numerous proteins, peptides, enzymes, and other macromolecules. Red blood cell (RBC)-based nanocarrier systems, known as erythrocyte nanovesicles, exhibit remarkable characteristics including prolonged circulation times, evasion of the immune system, gradual drug release, protection of drugs and biosensors from endogenous factors, targeted delivery, and applications in both therapeutic and diagnostic domains within biomedical sciences. Erythrocytes, the most prevalent circulating blood cells, have been thoroughly studied for biomimetic coatings on artificial nanocarriers owing to their enhanced biocompatibility, biodegradability, non-immunogenicity, and prolonged circulation in the bloodstream. Consequently, erythrocyte nanovehicles (ENV) has many applications, including drug transport, imaging, phototherapy, immunomodulation, sensing, and detection, which indicate substantial promise for therapeutic and diagnostic uses in various disorders. This paper covers recent advancements in the biomedical uses of ENV in cancer, infections, cardiovascular issues, and several other associated ailments particularly for biosensing. This paper also presents the RBC-mediated transport of nanobiosensors for bio-imaging at the single-cell level, enhanced medical diagnostics, and the analytical detection of biomolecules and cellular activity.
{"title":"Erythrocyte-derived nanosystems for biosensing: A green approach for analysis","authors":"Shivam Rajput , Rishabha Malviya , Sathvik Belagodu Sridhar , Tarun Wadhwa , Javedh Shareef","doi":"10.1016/j.jpbao.2025.100088","DOIUrl":"10.1016/j.jpbao.2025.100088","url":null,"abstract":"<div><div>Biosensors utilising nanotechnology are advancing swiftly and are extensively employed across various domains, including biomedicine, environmental monitoring, and analytical chemistry, where they have attained significant roles. Novel nanomaterials are being extensively designed and produced for prospective biosensing and theranostic uses. This review provides a comprehensive analysis of relevant literature from the past ten years, focusing on the use of nanoparticles in this context. The amalgamation of diagnostic biosensors with drug delivery systems for the administration of therapeutic agents presents significant potential in next-generation theranostic platforms. The controllable, precise, and safe delivery of diagnostic biosensing devices and therapeutic drugs to target tissues, organs, or cells is a crucial factor in the development of improved nanobiosensor-based theranostic systems. Recently, the utilisation of natural biological carriers in drug delivery systems has become one of the most extensively studied research issues. Erythrocytes, or red blood cells, may serve as carriers for a diverse array of pharmaceuticals, encompassing anticancer, antibacterial, antiviral, and anti-inflammatory agents, as well as numerous proteins, peptides, enzymes, and other macromolecules. Red blood cell (RBC)-based nanocarrier systems, known as erythrocyte nanovesicles, exhibit remarkable characteristics including prolonged circulation times, evasion of the immune system, gradual drug release, protection of drugs and biosensors from endogenous factors, targeted delivery, and applications in both therapeutic and diagnostic domains within biomedical sciences. Erythrocytes, the most prevalent circulating blood cells, have been thoroughly studied for biomimetic coatings on artificial nanocarriers owing to their enhanced biocompatibility, biodegradability, non-immunogenicity, and prolonged circulation in the bloodstream. Consequently, erythrocyte nanovehicles (ENV) has many applications, including drug transport, imaging, phototherapy, immunomodulation, sensing, and detection, which indicate substantial promise for therapeutic and diagnostic uses in various disorders. This paper covers recent advancements in the biomedical uses of ENV in cancer, infections, cardiovascular issues, and several other associated ailments particularly for biosensing. This paper also presents the RBC-mediated transport of nanobiosensors for bio-imaging at the single-cell level, enhanced medical diagnostics, and the analytical detection of biomolecules and cellular activity.</div></div>","PeriodicalId":100822,"journal":{"name":"Journal of Pharmaceutical and Biomedical Analysis Open","volume":"6 ","pages":"Article 100088"},"PeriodicalIF":0.0,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144841093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A robust and sensitive ultra-performance liquid chromatography (UPLC) method was developed and rigorously validated for the simultaneous quantification of rizatriptan, meloxicam, and their corresponding N-nitrosamine impurities in pharmaceutical dosage forms. Method development and optimization were conducted using a Box–Behnken Design to systematically investigate the effects of acetonitrile proportion, mobile phase flow rate, and pH on critical chromatographic responses, including retention time and tailing factor. Optimal separation was achieved with a mobile phase comprising 30 % v/v acetonitrile, a flow rate of 0.2 mL/min, and a pH of 2.5, resulting in well-resolved, symmetrical peaks. Validation performed in accordance with ICH guidelines confirmed excellent linearity (R² > 0.999) over the tested concentration ranges, low limits of detection (0.47–1.39 µg/mL), high precision (%RSD <2 %), and satisfactory accuracy (98–102 % recoveries). The method demonstrated robustness under deliberate minor variations of chromatographic parameters and maintained specificity by effectively resolving target analytes from degradation products during forced degradation studies. Sustainability and environmental impact were comprehensively assessed using ComplexGAPI, AGREE, AGREEprep, Analytical Eco-Scale, and Blue Applicability Grade Index metrics, all indicating high greenness and operational suitability. Application of the method to the commercial combination product Symbravo confirmed its capability for accurate quantification of active pharmaceutical ingredients and low-level nitrosamine impurities. Collectively, these findings underscore the method’s suitability for routine quality control, impurity profiling, and regulatory compliance in modern pharmaceutical analysis.
{"title":"A stability-indicating and environmentally sustainable UPLC method for simultaneous determination of rizatriptan, meloxicam, and related N-nitrosamine impurities","authors":"KiranKumar Chagarlamudi , Venkata Kanaka Srivani Maddala , Kumaraswamy Gandla","doi":"10.1016/j.jpbao.2025.100087","DOIUrl":"10.1016/j.jpbao.2025.100087","url":null,"abstract":"<div><div>A robust and sensitive ultra-performance liquid chromatography (UPLC) method was developed and rigorously validated for the simultaneous quantification of rizatriptan, meloxicam, and their corresponding N-nitrosamine impurities in pharmaceutical dosage forms. Method development and optimization were conducted using a Box–Behnken Design to systematically investigate the effects of acetonitrile proportion, mobile phase flow rate, and pH on critical chromatographic responses, including retention time and tailing factor. Optimal separation was achieved with a mobile phase comprising 30 % v/v acetonitrile, a flow rate of 0.2 mL/min, and a pH of 2.5, resulting in well-resolved, symmetrical peaks. Validation performed in accordance with ICH guidelines confirmed excellent linearity (R² > 0.999) over the tested concentration ranges, low limits of detection (0.47–1.39 µg/mL), high precision (%RSD <2 %), and satisfactory accuracy (98–102 % recoveries). The method demonstrated robustness under deliberate minor variations of chromatographic parameters and maintained specificity by effectively resolving target analytes from degradation products during forced degradation studies. Sustainability and environmental impact were comprehensively assessed using ComplexGAPI, AGREE, AGREEprep, Analytical Eco-Scale, and Blue Applicability Grade Index metrics, all indicating high greenness and operational suitability. Application of the method to the commercial combination product Symbravo confirmed its capability for accurate quantification of active pharmaceutical ingredients and low-level nitrosamine impurities. Collectively, these findings underscore the method’s suitability for routine quality control, impurity profiling, and regulatory compliance in modern pharmaceutical analysis.</div></div>","PeriodicalId":100822,"journal":{"name":"Journal of Pharmaceutical and Biomedical Analysis Open","volume":"6 ","pages":"Article 100087"},"PeriodicalIF":0.0,"publicationDate":"2025-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144841092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This study presents a detailed forced degradation profiling of lumateperone under stress conditions to develop a stability-indicating method capable of separating degradation products (DP-1 to DP-11), followed by their identification and characterization using hyphenated analytical techniques. Significant degradation was observed under oxidative, acidic, alkaline, and photolytic conditions. Oxidative stress generated an intensely colored quinone derivative (DP-2) as a major degradation product along with DP-3, DP-4, and DP-6. Alkaline hydrolysis yielded N-dealkylated and hydroxylated species (DP-1, DP-4, DP-5) and also produced a volatile degradation product, DP-7. Photolytic stress resulted in DP-2 and DP-8, whereas neutral hydrolysis led to the formation of DP-1, DP-2, DP-4, and DP-7. Notably, acidic hydrolysis in hydrochloric acid triggered dimer degradation product (DP-9) and chlorinated positional isomers of lumateperone (DP-10 and DP-11). The chemical structures of DP-1 to DP-6 and DP-8 to DP-11 were proposed by liquid chromatography-high-resolution mass spectrometry (LC-HRMS). DP-7 was identified as 1-(4-Fluorophenyl)ethanol using gas chromatography-mass spectrometry (GC–MS). The major degradation product, DP-2, was isolated and further characterized by nuclear magnetic resonance (NMR). A few DPs shared structural features with previously reported metabolites, suggesting a resemblance between chemical degradation and metabolic processes. The developed method was validated in accordance with ICH Q2(R1), demonstrating excellent linearity (r² > 0.999), accuracy, precision, specificity, and robustness. In silico toxicity analysis using ADMET Predictor® flagged four DPs (DP-1, DP-2, DP-5, and DP-6) with mutagenic alerts and predicted additional hepatotoxic, cardiotoxic, and receptor-mediated risks.These findings support formulation and quality management of lumateperone.
{"title":"Identification and characterization of forced degradation products of lumateperone tosylate by LC-HRMS, GC-MS, NMR, and in silico toxicity prediction","authors":"Nehal Bhatt , Devendra Sonaje , Vijiaya Madhyanapu Golla , Rahul Khemchandani , Roshitha K. R , Arun Kumar Gupta , Gananadhamu Samanthula","doi":"10.1016/j.jpbao.2025.100085","DOIUrl":"10.1016/j.jpbao.2025.100085","url":null,"abstract":"<div><div>This study presents a detailed forced degradation profiling of lumateperone under stress conditions to develop a stability-indicating method capable of separating degradation products (DP-1 to DP-11), followed by their identification and characterization using hyphenated analytical techniques. Significant degradation was observed under oxidative, acidic, alkaline, and photolytic conditions. Oxidative stress generated an intensely colored quinone derivative (DP-2) as a major degradation product along with DP-3, DP-4, and DP-6. Alkaline hydrolysis yielded N-dealkylated and hydroxylated species (DP-1, DP-4, DP-5) and also produced a volatile degradation product, DP-7. Photolytic stress resulted in DP-2 and DP-8, whereas neutral hydrolysis led to the formation of DP-1, DP-2, DP-4, and DP-7. Notably, acidic hydrolysis in hydrochloric acid triggered dimer degradation product (DP-9) and chlorinated positional isomers of lumateperone (DP-10 and DP-11). The chemical structures of DP-1 to DP-6 and DP-8 to DP-11 were proposed by liquid chromatography-high-resolution mass spectrometry (LC-HRMS). DP-7 was identified as 1-(4-Fluorophenyl)ethanol using gas chromatography-mass spectrometry (GC–MS). The major degradation product, DP-2, was isolated and further characterized by nuclear magnetic resonance (NMR). A few DPs shared structural features with previously reported metabolites, suggesting a resemblance between chemical degradation and metabolic processes. The developed method was validated in accordance with ICH Q2(R1), demonstrating excellent linearity (r² > 0.999), accuracy, precision, specificity, and robustness. <em>In silico</em> toxicity analysis using ADMET Predictor® flagged four DPs (DP-1, DP-2, DP-5, and DP-6) with mutagenic alerts and predicted additional hepatotoxic, cardiotoxic, and receptor-mediated risks.These findings support formulation and quality management of lumateperone.</div></div>","PeriodicalId":100822,"journal":{"name":"Journal of Pharmaceutical and Biomedical Analysis Open","volume":"6 ","pages":"Article 100085"},"PeriodicalIF":0.0,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144771384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-07-22DOI: 10.1016/j.jpbao.2025.100081
Almir Custodio Batista Junior, Yuri Arrates Rocha, Andrea Rodrigues Chaves
N-Nitrosamines (NAs) are classified as potent mutagenic impurities, raising substantial concerns due to their presence in various consumer products, including pharmaceuticals products. The detection of NAs in valsartan-containing medicines in 2018 led regulatory agencies to establish strict guidelines for permissible levels in drug formulations. The standard-gold analytical techniques for NAs determination have been chromatographic techniques (liquid and gas chromatography) coupled with mass spectrometry system, which present higher sensibility and accuracy for target NAs. However, accurate determination of NAs in medicines remains challenging due to their trace-level concentrations and susceptibility to matrix effects, carryover, and contamination of the analytical instrumentation, emphasizing the need for robust sample preparation strategies. Traditional sample preparation methods, although effective, often involve high consumption of solvents, samples, and extraction phases, along with substantial waste generation. In response, miniaturized sample preparation techniques have emerged as sustainable alternatives, offering reduced solvent usage, minimal sample requirements, and lower energy consumption, all while maintaining analytical performance. These green approaches not only align with sustainable analytical practices but also enhance efficiency and environmental compliance in pharmaceutical analysis. This review provides a comprehensive overview of recent advancements in miniaturized sample preparation strategies for the determination of NAs in pharmaceutical products, highlighting their analytical merits and potential for regulatory adoption.
n -亚硝胺（na）被归类为强致突变杂质，由于其存在于各种消费品中，包括药品，引起了极大的关注。2018年在含有缬沙坦的药物中检测到NAs，导致监管机构制定了严格的药物配方允许含量指导方针。测定NAs的标准金分析技术是色谱技术（液相和气相色谱）与质谱联用技术，对目标NAs具有较高的灵敏度和准确性。然而，药物中NAs的准确测定仍然具有挑战性，因为它们的痕量浓度和对基质效应、携带和分析仪器污染的敏感性，强调需要可靠的样品制备策略。传统的样品制备方法虽然有效，但往往涉及高溶剂，样品和提取相的消耗，以及大量的废物产生。因此，小型化样品制备技术已经成为可持续的替代方案，提供了更少的溶剂使用，最小的样品要求，更低的能源消耗，同时保持分析性能。这些绿色方法不仅与可持续分析实践相一致，而且还提高了药物分析的效率和环境合规性。本文综述了用于测定药品中NAs的小型化样品制备策略的最新进展，强调了它们的分析优点和监管采用的潜力。
{"title":"Miniaturized sample preparation strategies for the determination of N-nitrosamines in pharmaceutical products: A comprehensive review","authors":"Almir Custodio Batista Junior, Yuri Arrates Rocha, Andrea Rodrigues Chaves","doi":"10.1016/j.jpbao.2025.100081","DOIUrl":"10.1016/j.jpbao.2025.100081","url":null,"abstract":"<div><div>N-Nitrosamines (NAs) are classified as potent mutagenic impurities, raising substantial concerns due to their presence in various consumer products, including pharmaceuticals products. The detection of NAs in valsartan-containing medicines in 2018 led regulatory agencies to establish strict guidelines for permissible levels in drug formulations. The standard-gold analytical techniques for NAs determination have been chromatographic techniques (liquid and gas chromatography) coupled with mass spectrometry system, which present higher sensibility and accuracy for target NAs. However, accurate determination of NAs in medicines remains challenging due to their trace-level concentrations and susceptibility to matrix effects, carryover, and contamination of the analytical instrumentation, emphasizing the need for robust sample preparation strategies. Traditional sample preparation methods, although effective, often involve high consumption of solvents, samples, and extraction phases, along with substantial waste generation. In response, miniaturized sample preparation techniques have emerged as sustainable alternatives, offering reduced solvent usage, minimal sample requirements, and lower energy consumption, all while maintaining analytical performance. These green approaches not only align with sustainable analytical practices but also enhance efficiency and environmental compliance in pharmaceutical analysis. This review provides a comprehensive overview of recent advancements in miniaturized sample preparation strategies for the determination of NAs in pharmaceutical products, highlighting their analytical merits and potential for regulatory adoption.</div></div>","PeriodicalId":100822,"journal":{"name":"Journal of Pharmaceutical and Biomedical Analysis Open","volume":"6 ","pages":"Article 100081"},"PeriodicalIF":0.0,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144704536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A novel, green, and robust Liquid chromatography–tandem mass spectrometry (LC–MS/MS) method was developed and validated for the simultaneous quantification of sulopenem etzadroxil and probenecid in rat plasma, with application to pharmacokinetic studies. Method development was guided by a Box–Behnken Design and response surface methodology, optimizing key chromatographic variables—ethanol proportion (40–60 %), flow rate (0.8–1.2 mL/min), and mobile phase pH (2.8–3.2)—to achieve maximum resolution, peak area, and analytical reproducibility. Chromatographic separation was performed on a Kromasil C18 column using ethanol and 0.1 % TFA (50:50, v/v) as the mobile phase. Mass spectrometric detection employed selected reaction monitoring in positive ion mode using an LC-MS/MS instrument. The method exhibited excellent linearity (10–400 ng/mL), low limits of detection (LOD: ∼3 ng/mL), and quantification (LOQ: ∼9 ng/mL) for both analytes, with recovery rates > 93 % and %CVs < 15 %. Greenness and sustainability assessments using analytical GREEnness metric (AGREE), analytical GREEnness metric for sample PREParation (AGREEprep), complementary green analytical procedure index (ComplexGAPI), Eco-Scale, and Blue applicability grade index (BAGI) confirmed the method’s environmental compatibility and analytical reliability, with scores exceeding 65 across all tools. This validated method demonstrates high sensitivity, reproducibility, and environmental responsibility, rendering it suitable for routine bioanalytical and pharmacokinetic applications.
{"title":"A green and robust LC–MS/MS bioanalytical method for sulopenem etzadroxil and probenecid: Optimization, validation, and pharmacokinetic application","authors":"Niloufer Tasnim Khazi, Kumaraswamy Gandla, Lalitha Repudi","doi":"10.1016/j.jpbao.2025.100083","DOIUrl":"10.1016/j.jpbao.2025.100083","url":null,"abstract":"<div><div>A novel, green, and robust Liquid chromatography–tandem mass spectrometry (LC–MS/MS) method was developed and validated for the simultaneous quantification of sulopenem etzadroxil and probenecid in rat plasma, with application to pharmacokinetic studies. Method development was guided by a Box–Behnken Design and response surface methodology, optimizing key chromatographic variables—ethanol proportion (40–60 %), flow rate (0.8–1.2 mL/min), and mobile phase pH (2.8–3.2)—to achieve maximum resolution, peak area, and analytical reproducibility. Chromatographic separation was performed on a Kromasil C18 column using ethanol and 0.1 % TFA (50:50, v/v) as the mobile phase. Mass spectrometric detection employed selected reaction monitoring in positive ion mode using an LC-MS/MS instrument. The method exhibited excellent linearity (10–400 ng/mL), low limits of detection (LOD: ∼3 ng/mL), and quantification (LOQ: ∼9 ng/mL) for both analytes, with recovery rates > 93 % and %CVs < 15 %. Greenness and sustainability assessments using analytical GREEnness metric (AGREE), analytical GREEnness metric for sample PREParation (AGREEprep), complementary green analytical procedure index (ComplexGAPI), Eco-Scale, and Blue applicability grade index (BAGI) confirmed the method’s environmental compatibility and analytical reliability, with scores exceeding 65 across all tools. This validated method demonstrates high sensitivity, reproducibility, and environmental responsibility, rendering it suitable for routine bioanalytical and pharmacokinetic applications.</div></div>","PeriodicalId":100822,"journal":{"name":"Journal of Pharmaceutical and Biomedical Analysis Open","volume":"6 ","pages":"Article 100083"},"PeriodicalIF":0.0,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144695367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-07-21DOI: 10.1016/j.jpbao.2025.100084
Yue Zhang, Joëlle Widart, Eric Ziemons, Philippe Hubert, Cédric Hubert
N-nitrosamines have been a concern for decades due to their potential mutagenicity and widespread occurrence across various matrices. While evidence suggests carcinogenicity in animals, their potential carcinogenicity in humans has prompted their initial inclusion in the “cohort of concern” since in ICH M7(R1), and the current ICH M7(R2) guideline is now in effect. Intensified control of N-nitrosamines began in 2018 following the detection of N-nitrosodimethylamine in valsartan-containing products. Subsequent investigations revealed N-nitrosamine contamination across multiple drug classes, triggering widespread recalls, withdrawals, and regulatory actions. Recently, the emergence of N-nitrosamine drug substance-related impurities and drug linker-related impurities has drawn additional regulatory attention. This review presents the methodologies used to determine the acceptable daily intake of N-nitrosamines and traces the evolution of regulatory guidelines, offering a comparative analysis of the 3-step investigation approaches adopted by the European Medicines Agency and Food and Drug Administration. It provides a comprehensive examination of potential root causes for N-nitrosamine contamination, outlines the analytical requirements for confirmatory testing, as well as mitigation strategies to prevent or minimize contamination. Additionally, the review summarizes risk assessment tools used to predict N-nitrosamine formation. By presenting a comprehensive workflow for impurity investigations, this review aims to assist industrial stakeholders in managing N-nitrosamine risks, ensuring regulatory compliance, and safeguarding public health.
n -亚硝胺由于其潜在的诱变性和广泛存在于各种基质中，几十年来一直受到关注。虽然有证据表明它们对动物具有致癌性，但它们对人类的潜在致癌性促使它们自ICH M7（R1）以来首次被列入“关注队列”，目前的ICH M7（R2）指南现已生效。在缬沙坦产品中检测到n-亚硝基二甲胺后，2018年开始加强对n-亚硝胺的控制。随后的调查显示，n -亚硝胺污染了多种药物类别，引发了大范围的召回、下架和监管行动。最近，n -亚硝胺类原料药相关杂质和药物连接物相关杂质的出现引起了监管部门的额外关注。本综述介绍了用于确定n -亚硝胺每日可接受摄入量的方法，并追溯了监管指南的演变，对欧洲药品管理局和食品药品管理局采用的三步调查方法进行了比较分析。它全面审查了n -亚硝胺污染的潜在根本原因，概述了验证性测试的分析要求，以及防止或尽量减少污染的缓解战略。此外，综述总结了用于预测n -亚硝胺形成的风险评估工具。通过介绍杂质调查的综合工作流程，本综述旨在帮助工业利益相关者管理n -亚硝胺风险，确保法规合规性，并维护公众健康。
{"title":"N-nitrosamine risk assessment in pharmaceuticals: Where are we from a regulatory point of view in 2025?","authors":"Yue Zhang, Joëlle Widart, Eric Ziemons, Philippe Hubert, Cédric Hubert","doi":"10.1016/j.jpbao.2025.100084","DOIUrl":"10.1016/j.jpbao.2025.100084","url":null,"abstract":"<div><div><em>N</em>-nitrosamines have been a concern for decades due to their potential mutagenicity and widespread occurrence across various matrices. While evidence suggests carcinogenicity in animals, their potential carcinogenicity in humans has prompted their initial inclusion in the “cohort of concern” since in ICH M7(R1), and the current ICH M7(R2) guideline is now in effect. Intensified control of <em>N</em>-nitrosamines began in 2018 following the detection of <em>N</em>-nitrosodimethylamine in valsartan-containing products. Subsequent investigations revealed <em>N</em>-nitrosamine contamination across multiple drug classes, triggering widespread recalls, withdrawals, and regulatory actions. Recently, the emergence of <em>N</em>-nitrosamine drug substance-related impurities and drug linker-related impurities has drawn additional regulatory attention. This review presents the methodologies used to determine the acceptable daily intake of <em>N</em>-nitrosamines and traces the evolution of regulatory guidelines, offering a comparative analysis of the 3-step investigation approaches adopted by the European Medicines Agency and Food and Drug Administration. It provides a comprehensive examination of potential root causes for <em>N</em>-nitrosamine contamination, outlines the analytical requirements for confirmatory testing, as well as mitigation strategies to prevent or minimize contamination. Additionally, the review summarizes risk assessment tools used to predict <em>N</em>-nitrosamine formation. By presenting a comprehensive workflow for impurity investigations, this review aims to assist industrial stakeholders in managing <em>N</em>-nitrosamine risks, ensuring regulatory compliance, and safeguarding public health.</div></div>","PeriodicalId":100822,"journal":{"name":"Journal of Pharmaceutical and Biomedical Analysis Open","volume":"6 ","pages":"Article 100084"},"PeriodicalIF":0.0,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144695369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-07-21DOI: 10.1016/j.jpbao.2025.100082
Somar Khalil, Michel Plisnier
Host cell proteins (HCPs) are critical quality attributes that can impact the safety, efficacy, and quality of biotherapeutics. Label-free shotgun proteomics is a vital approach for HCP monitoring, yet the choice of tandem mass spectrometry (MS/MS) search algorithms directly influences identification depth and quantification reliability. In this study, six prominent MS/MS search tools (Mascot, MaxQuant, SpectroMine, FragPipe, Byos, and PEAKS) were systematically benchmarked for their performance on complex samples spiked with isotopically labeled proteins from Chinese hamster ovary cells. The data were acquired using trapped ion mobility spectrometry and parallel accumulation–serial fragmentation in data-dependent acquisition mode. Key performance metrics, including peptide and protein identifications, data extraction precision, fold-change (FC) accuracy, linearity, and measurement trueness, were evaluated. A Bayesian modeling framework with Hamiltonian Monte Carlo sampling was employed to robustly estimate FC means and variances, alongside local false discovery rates through posterior probability calibration. Bayesian decision theory, implemented via expected utility maximization, was used to balance accuracy against posterior uncertainty and provide a probabilistic assessment of each tool’s performance. Through this cumulative analysis, variability across tools was observed: Byos and SpectroMine excelled in quantitative accuracy with minimal bias, FragPipe provided high precision and quantifiability, PEAKS offered deep protein coverage, Mascot showed strong trueness, and MaxQuant exhibited moderate identification performance with greater variability at lower spike levels. This study establishes a rigorous, data-driven framework for tool benchmarking and offers guidance for selecting MS/MS tools suited to HCP monitoring in biopharmaceutical development.
{"title":"Comparative analysis of MS/MS search algorithms in label-free shotgun proteomics for monitoring host-cell proteins using trapped ion mobility and ddaPASEF","authors":"Somar Khalil, Michel Plisnier","doi":"10.1016/j.jpbao.2025.100082","DOIUrl":"10.1016/j.jpbao.2025.100082","url":null,"abstract":"<div><div>Host cell proteins (HCPs) are critical quality attributes that can impact the safety, efficacy, and quality of biotherapeutics. Label-free shotgun proteomics is a vital approach for HCP monitoring, yet the choice of tandem mass spectrometry (MS/MS) search algorithms directly influences identification depth and quantification reliability. In this study, six prominent MS/MS search tools (Mascot, MaxQuant, SpectroMine, FragPipe, Byos, and PEAKS) were systematically benchmarked for their performance on complex samples spiked with isotopically labeled proteins from Chinese hamster ovary cells. The data were acquired using trapped ion mobility spectrometry and parallel accumulation–serial fragmentation in data-dependent acquisition mode. Key performance metrics, including peptide and protein identifications, data extraction precision, fold-change (FC) accuracy, linearity, and measurement trueness, were evaluated. A Bayesian modeling framework with Hamiltonian Monte Carlo sampling was employed to robustly estimate FC means and variances, alongside local false discovery rates through posterior probability calibration. Bayesian decision theory, implemented via expected utility maximization, was used to balance accuracy against posterior uncertainty and provide a probabilistic assessment of each tool’s performance. Through this cumulative analysis, variability across tools was observed: Byos and SpectroMine excelled in quantitative accuracy with minimal bias, FragPipe provided high precision and quantifiability, PEAKS offered deep protein coverage, Mascot showed strong trueness, and MaxQuant exhibited moderate identification performance with greater variability at lower spike levels. This study establishes a rigorous, data-driven framework for tool benchmarking and offers guidance for selecting MS/MS tools suited to HCP monitoring in biopharmaceutical development.</div></div>","PeriodicalId":100822,"journal":{"name":"Journal of Pharmaceutical and Biomedical Analysis Open","volume":"6 ","pages":"Article 100082"},"PeriodicalIF":0.0,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144695366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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