Journal Of Pharmaceutical And Biomedical Analysis[JOURNAL]
Sun
200 papers
Development and validation of a sensitive UPLC-MS/MS platform for comprehensive bile acid profiling in multiple biological matrices: Application to a 17α-ethinylestradiol-induced cholestatic rat model.
Jiang G, Fu Y, Zhang P … +5 more , Wu J, Zhao G, Chen W, Xu Y, Wang R
J Pharm Biomed Anal · 2026 Sep · PMID 42085938 · Publisher ↗
Bile acids are crucial indicators for the diagnosis of liver diseases, including cholestasis, which necessitates robust and versatile analytical methods for comprehensive analysis. This study presents a validated UPLC-MS...
Bile acids are crucial indicators for the diagnosis of liver diseases, including cholestasis, which necessitates robust and versatile analytical methods for comprehensive analysis. This study presents a validated UPLC-MS/MS method for the quantitative determination of 23 bile acids in rat plasma, ileal tissues, and feces, encompassing free primary and secondary bile acids as well as taurine-conjugated and glycine-conjugated bile acids. All bile acids were qualitatively and quantitatively assessed within 24 min. The method demonstrated detection limits of 0.01-0.1 ng/mL, and quantification limits of 0.1-1 ng/mL. Performance evaluation demonstrated excellent specificity and good method robustness. Both intra-day and inter-day precision were below 12.4%, with accuracy ranging from 86.8% to 113%. Extraction recoveries were 90.7-108% with RSD of 1.11-11.9%, while matrix effects were 93.5-109% with RSD of 0.30-11.6%, indicating high extraction efficiency and negligible matrix interference. The analytes were stable under the tested conditions, with stability values from 86.1% to 113%. In an estrogen-induced cholestatic rat model, the UPLC-MS/MS method detected increased conjugated bile acids in plasma and a disturbed primary-to-secondary bile acid ratio in ileal and fecal samples, indicating impaired enterohepatic circulation. The method was fully validated in accordance with the Guideline on Bioanalytical Method Validation and demonstrated reliable, stable, and consistent quantification of bile acids across complex biological matrices. This work supports mechanistic studies of cholestasis and facilitates the identification of potential clinical biomarkers.
Assessing valproate-induced changes in NADH levels in patients with type 2 diabetes using a silver nanoparticle-based method: An in-vitro study.
Esmaeeli S, Khoubnasabjafari M, Rahimpour E … +1 more , Jouyban A
J Pharm Biomed Anal · 2026 Sep · PMID 42085937 · Publisher ↗
Type 2 diabetes is a common metabolic disease that is associated with increased oxidative stress and impaired nicotinamide-adenine dinucleotide (NAD/NADH) ratio. NADH, as a key metabolic biomarker, plays a crucial role i...
Type 2 diabetes is a common metabolic disease that is associated with increased oxidative stress and impaired nicotinamide-adenine dinucleotide (NAD/NADH) ratio. NADH, as a key metabolic biomarker, plays a crucial role in assessing oxidative status. Herein, a spectrophotometric method based on in-situ synthesis of silver nanoparticles (Ag NPs) was validated for the quantification of NADH. In this method, NADH, acting as a reductant, reduced Ag to Ag, resulting in Ag NPs formation that exhibited a specific optical absorption at 425 nm. The plasma from patients with type 2 diabetes was collected and analyzed by the aforementioned method for NADH level. Then, each plasma sample was treated in-vitro with an appropriate concentration of sodium valproate in the therapeutic range, and finally, their NADH concentrations were measured by the developed method. The method detected NADH in plasma with LOD of 0.05 µmol/L and good linearity (R² = 0.9965) within a range of 0.22-3.8 µmol/L. The assay demonstrated acceptable precision, with intra-day and inter-day repeatability of 4.6% and 7.4% RSD, respectively. The results of in-vitro studies indicated that the level of NADH decreased following sodium valproate addition. It is noteworthy that this decrease was proportional to the increasing concentration of sodium valproate, suggesting the influence of this antiepileptic drug on the oxidative status in the plasma of patients with type 2 diabetes.
Integrated chiral separation, recognition mechanism and enantioselective pharmacokinetic study of tetrahydrojatrorrhizine enantiomers by HPLC-MS/MS method.
Qi C, Song J, Lv L … +4 more , Yin Y, Wang S, Li M, Li Q
J Pharm Biomed Anal · 2026 Sep · PMID 42068739 · Publisher ↗
A robust HPLC method employing a polysaccharide-based chiral stationary phase was developed and optimized for the enantiomeric separation of tetrahydrojatrorrhizine. Investigations into the effects of chromatographic con...
A robust HPLC method employing a polysaccharide-based chiral stationary phase was developed and optimized for the enantiomeric separation of tetrahydrojatrorrhizine. Investigations into the effects of chromatographic conditions on enantiomeric separation revealed that a specific mobile phase, comprising methanol and ammonium acetate solution, significantly enhanced enantioselectivity with a resolution of 1.89 at a lower column temperature. Thermodynamic analysis based on van't Hoff plots was carried out, which demonstrated a clear enthalpy-driven potential for chiral recognition, suggesting binding interactions played the dominant role in enantiomeric separation. To elucidate molecular mechanisms of chiral recognition, the complementary docking simulation was also performed, identifying that the observed enantioselectivity originated from differences in the key interactions, including hydrogen bond, π-π stacking, and steric hindrance. Additionally, a chiral HPLC-MS/MS method was fully validated for the determination of tetrahydrojatrorrhizine enantiomers in rat plasma, and applied to a preliminary enantioselective pharmacokinetic study. The results showed significantly different pharmacokinetic profiles between the two enantiomers, highlighting that the area under the curve of S-(-)-tetrahydrojatrorrhizine was statistically higher than that of R-(+)-tetrahydrojatrorrhizine. The integrated work presented herein provided a reliable analytical method and mechanistic insights into chiral recognition of tetrahydrojatrorrhizine enantiomers, supporting the precise evaluation of enantiomeric behaviors in vivo.
Evaluation of the impact of uncertainty on mass balance applied to stress testing studies.
Salles AK, Lourenço FR
J Pharm Biomed Anal · 2026 Sep · PMID 42061926 · Publisher ↗
Forced degradation studies on active pharmaceutical ingredients (APIs) and drug products allow for the assessment of degradation products that may emerge during stability studies, as well as challenge the ability of the...
Forced degradation studies on active pharmaceutical ingredients (APIs) and drug products allow for the assessment of degradation products that may emerge during stability studies, as well as challenge the ability of the stability-indicating method to assess changes in drug content in the presence of degradation products. A key parameter for evaluating the quality of such methods is Mass Balance (MB), which assesses the analytical method's ability to quantify formed impurities by comparing the sum of the contents of the API and the degradation products formed with the initial condition. A perfect MB, that is, a sum equal to 100% relative to the initial value, is often unattainable due to several reasons, including limited trueness and precision of the analytical method. Measurement uncertainty evaluation can be a viable tool for this purpose, as it allows a metrological comparison between the degradation products formed and the initial amount of the drug. This study aims to investigate the use of measurement uncertainty information applied to a forced degradation study of acetylsalicylic acid to salicylic acid, both quantified by UV-Vis spectroscopy. The data was evaluated using the Monte Carlo Method (MCM), implemented in Python 3.13.5, the software was named 'MBSim'. Based on Monte Carlo simulations, considering the content data of salicylic acid and acetylsalicylic acid and their respective measurement uncertainties, a MB interval was obtained that allows the assessment of the similarity between the initial and final distributions. The comparison was performed using by assessing p-value through Two One-Sided Tests (TOST), degree of overlap (from 0.04 to 0.97) and the calculation of Cohen's d (from -4.14-1.84), and these tools proved to be promising for supporting the understanding of MB in forced degradation studies.
Ammonium adduct-triggered MS³ detection and post-column infusion in UPC²-MS³: A green strategy for sensitive tissue distribution study of methoxy polyethylene glycol with 6 subunits in zebrafish.
Feng S, Deng Y, Zhang J … +5 more , Liu J, Zhou X, Xi Y, Yin L, Shi M
J Pharm Biomed Anal · 2026 Sep · PMID 42061925 · Publisher ↗
Short-chain polyethylene glycol derivatives, such as methoxy polyethylene glycol with 6 subunits (M‑PEG₆‑OH), are extensively utilized excipients and building blocks, yet their in vivo biodistribution and associated safe...
Short-chain polyethylene glycol derivatives, such as methoxy polyethylene glycol with 6 subunits (M‑PEG₆‑OH), are extensively utilized excipients and building blocks, yet their in vivo biodistribution and associated safety profiles remain insufficiently characterized. To address this knowledge gap, this study developed a novel, environmentally conscious analytical platform based on ultra‑performance convergence chromatography‑tandem mass spectrometry (UPC²‑MS³) for the sensitive quantification of M‑PEG₆‑OH in zebrafish tissues. A key methodological innovation involved the selective formation and detection of ammonium adducts ([M+NH₄]⁺) as precursor ions, coupled with a post‑column infusion strategy. This combined approach effectively mitigated ion suppression and significantly enhanced ionization efficiency, yielding an average 5‑fold increase in analytical signal response. The fully validated method achieved rapid and baseline separation of the analyte within 1.5 min. Its successful application to a tissue distribution study revealed distinct, time‑dependent accumulation profiles, with the highest levels observed in gill, followed by liver and muscle tissues. Furthermore, the methodology was rigorously evaluated using established metric systems, demonstrating excellent environmental sustainability (AGREE score = 0.62) and outstanding practical applicability (BAGI score = 72.5). This work provides crucial insights into the tissue‑specific disposition of short‑chain PEG derivatives and establishes a sustainable, high‑performance analytical framework for the safety evaluation of PEGylated compounds.
Optimizing LOD/LOQ and sample consumption during analytical ultracentrifugation to characterize AAV gene therapy vectors.
Richter K, Wurm C, Hawe A … +7 more , Menzen T, Strasser K, Bauer J, Salomon M, Sternisha SM, VerHeul R, Bhattacharya A
J Pharm Biomed Anal · 2026 Sep · PMID 42055478 · Publisher ↗
Production and development of adeno-associated viruses (AAV) for gene therapy applications requires sophisticated analytical methods to assess critical quality attributes of the product. A popular method providing releva...
Production and development of adeno-associated viruses (AAV) for gene therapy applications requires sophisticated analytical methods to assess critical quality attributes of the product. A popular method providing relevant information on the loading status of the AAV capsid is sedimentation velocity analytical ultracentrifugation (SV-AUC). While multiwavelength SV-AUC, used along with extinction coefficients for different capsid species, delivers the relative percentages of empty, partially and filled AAV capsids, it does so at the cost of high sample consumption (typically 400 µl at ∼9*10 viral particles/ml) and therefore high expense. We investigated the SV-AUC method for AAV characterization at three wavelengths and determined a LOQ of 7.7% empty capsids with standard SEDFIT analysis, which can be improved by using the GUSSI integration package or automated SEDFIT workflows with predefined integration ranges to 2.3%. Beyond that we find that SV-AUC allows adaptation of the method to low sample consumption based on reduced filling volume and reduced sample concentration. For this, we tested result consistency at up to 50-fold reduction of AAV particle concentration compared to standard conditions, and a 3-fold reduction of sample volume. In these measurements, it remained possible to obtain several critical sample parameters, such as reliable values for empty and filled capsid contents and values for AAV concentrations despite the reduced sample amounts. Based on these data, sample consumption can be reduced by a factor of 20 with few setbacks, which mitigates one of the main disadvantages in the usage of SV-AUC for the characterization of AAV samples.
Systemic defense against oxidative stress - The role of iron imbalance revealed by multiomics mechanisms leading to urosepsis.
Wityk P, Raczak-Gutknecht J, Krawczyk B … +10 more , Biesemans M, Bronk M, Waszczuk-Jankowska M, Siemiński M, Sokołowska E, Szypenbejl J, Brzezińska W, Jewstafiew M, Gawrycka P, Markuszewski MJ
J Pharm Biomed Anal · 2026 Sep · PMID 42055477 · Publisher ↗
Urinary Tract Infections (UTIs) and urosepsis represent significant challenges in clinical medicine, necessitating a deeper understanding of the molecular intricacies underlying these conditions. In this study, we employ...
Urinary Tract Infections (UTIs) and urosepsis represent significant challenges in clinical medicine, necessitating a deeper understanding of the molecular intricacies underlying these conditions. In this study, we employed a multi-omics approach to elucidate the molecular landscape associated with UTIs and urosepsis, with a specific focus on ferroptosis and oxidative stress. Through integrative analysis of metabolomic, proteomic, and genetic data, we identified potential bacterial and human biomarkers linked to iron sequestration, oxidative damage, and dysregulated pathways associated with the progression and severity of UTIs and urosepsis. Elevated levels of glutathione, iron-handling proteins, and pro-inflammatory cytokines: Interleukin-6, Interleukin-8 suggest a mechanistic link between oxidative stress and ferroptosis in urosepsis. Importantly, our study highlights the role of oxidative damage in exacerbating tissue injury and systemic dysfunction during the progression of sepsis. We also identified 5,6-Dihydroxyindole-2-carboxylic acid as a novel biomarker for urosepsis, indicating that oxidative stress and iron metabolism dysregulation may extend beyond standard organs to influence broader systemic responses. This metabolite may serve as an early indicator for detecting and differenting of urosepsis from uncomplicated UTIs, providing a valuable tool to improve diagnostic precision and patient outcomes.
Mechanism of Qibai Pingfei Capsule in ameliorating COPD-associated inflammation via the ABCA3/PPARγ/NF-κB pathway: A serum-targeted metabolomics and lipidomics study.
Tang S, Liu M, Gao Y … +7 more , Xie J, Da W, Yang Q, Tong X, Fang X, Li Z, Zhu J
J Pharm Biomed Anal · 2026 Sep · PMID 42048924 · Publisher ↗
Chronic obstructive pulmonary disease (COPD) is a global health issue driven by chronic inflammation. Although Qibai Pingfei Capsule (QBPF) shows clinical efficacy in COPD, its multi-component, multi-target nature compli...
Chronic obstructive pulmonary disease (COPD) is a global health issue driven by chronic inflammation. Although Qibai Pingfei Capsule (QBPF) shows clinical efficacy in COPD, its multi-component, multi-target nature complicates mechanistic studies. A COPD rat model was established using smoking, hypoxia, and swimming. Metabolomics and lipidomics based on ultra-high performance liquid chromatography coupled with electrospray ionization triple quadrupole-linear ion trap mass spectrometry (UHPLC-ESI-QTRAP-MS) revealed that QBPF alleviated COPD-associated metabolic disruptions, particularly in energy, amino acid, and lipid metabolism. Multivariate statistical analysis, cluster analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis intended to obtain ATP binding cassette subfamily A member 3 (ABCA3) as a key target. Western blot (WB) analysis, enzyme-linked immunosorbent assay (ELISA), and immunohistochemistry (IHC) confirmed that QBPF upregulated the expression of ABCA3 and peroxisome proliferator-activated receptor gamma (PPARγ) in COPD rats, downregulated p-nuclear factor kappa B p65 (p-p65), and subsequently downregulated the expression of inflammatory factors such as interleukin-1 beta (IL-1β) and interleukin-17A (IL-17A), thereby alleviating COPD pulmonary inflammation. After transfection with small interfering RNA (siRNA) ABCA3, the expression of ABCA3 was knocked down and the upregulation of PPARγ by QBPF was weakened, thereby affecting its inhibitory effects on p65, IL-1β, and IL-17A. Our research results indicated that QBPF could upregulate the expression of ABCA3, leading to an increase in PPARγ and a decrease in p-p65, ultimately improving pulmonary inflammation in COPD.
Pharmacokinetics and qualitative metabolite profiling of major alkaloids in rats after acupoint administration of Xiatianwu Injection.
Zhang H, Zhao Y, Liu H … +7 more , Yu J, Wu K, Yi Y, Yuan L, Zhou H, Yan J, Jiang H
J Pharm Biomed Anal · 2026 Sep · PMID 42048923 · Publisher ↗
Xiatianwu (XTW) Injection, derived from Corydalis Decumbentis Rhizoma, is clinically utilized to promote circulation and alleviate pain. However, its effective components and pharmacokinetic profile have yet to be elucid...
Xiatianwu (XTW) Injection, derived from Corydalis Decumbentis Rhizoma, is clinically utilized to promote circulation and alleviate pain. However, its effective components and pharmacokinetic profile have yet to be elucidated. In the present study, 46 components, including 32 alkaloids, were identified in XTW Injection, of which 19 alkaloids were also detected in post-dose rat plasma by UPLC-QTOF analysis. Then a UPLC-QqQ assay was developed to determine ten alkaloids (corydalmine, corypalmine, columbamine, jatrorrhizine, palmatine, tetrahydropalmatine, protopine, allocryptopine, muramine, bicuculline) in rat plasma. Chromatographic separation was achieved on an ACQUITY UPLC HSS T3 column with 0.1% formic acid in water and acetonitrile as the mobile phases. The method showed satisfactory selectivity, linearity, matrix effects, precision, accuracy, and dilution integrity, and the samples showed sufficient stability. The validated method was successfully applied to the pharmacokinetic study in rats after acupoint administration of XTW Injection at three doses. The study revealed that most quantified alkaloids were rapidly absorbed. The C and AUC were positively related to the doses. Protopine, tetrahydropalmatine, and bicuculline showed higher plasma exposure, while tetrahydropalmatine, corypalmine and bicuculline exhibited higher dose-normalized C and AUC. Metabolites of the higher-exposure alkaloids (protopine, tetrahydropalmatine, and bicuculline) were tentatively identified by UPLC-QTOF in rat plasma, urine, bile, and feces, with 19, 25, and 7 annotated metabolites, respectively, formed mainly via O-demethylation, demethylenation, or hydroxylation, followed by glucuronidation or sulfation. This study will contribute to elucidating potential active components, the pharmacological mechanisms, and providing a basis for dose optimization.
Integrated LC-HRMS/MS-based metabolomics and in vitro and in vivo bioassays for comparative evaluation of two ethnomedicinal Paris species and their official counterparts.
Yu T, Sun Y, Qiu FN … +4 more , Liu K, Liu CL, Pu QY, Li HJ
J Pharm Biomed Anal · 2026 Sep · PMID 42030706 · Publisher ↗
Paris species, known as "Chonglou" in traditional Chinese medicine, have been used clinically for millennia. Nevertheless, the variation patterns of their chemical constituents and biological activities among different s...
Paris species, known as "Chonglou" in traditional Chinese medicine, have been used clinically for millennia. Nevertheless, the variation patterns of their chemical constituents and biological activities among different species are still poorly understood and urgently need to be elucidated. Current research has largely focused on a few pharmacopoeial species, while many with ethnomedicinal value remain scientifically unexplored. This study presents the first integrated metabolomic and pharmacological comparison of two pharmacopoeial species, P. polyphylla Smith var. chinensis (PPC) and P. polyphylla Smith var. yunnanensis (PPY), with two ethnomedicinal species, P. thibetica France (PT) and P. fargesii France (PF). A comprehensive phytochemical profile was established using UPLC-Q-TOF-MS/MS, identifying 119 compounds, 85.7% of which were steroidal saponins. Significant inter-species variation in total saponin content was observed, with PF showing the highest average. Multivariate statistical analysis successfully identified species-specific markers and revealed unexpected chemotaxonomic affinities. Pharmacologically, all four species exhibited significant dual bioactivities. They demonstrated potent hemostatic effects, significantly reducing tail bleeding time and directly inducing platelet aggregation. Concurrently, the extracts showed considerable anti-hepatocarcinoma activity. Mechanistically, this anti-cancer effect involved the induction of S-phase cell cycle arrest and apoptosis, which were associated with down-regulation of Bcl-2 and suppression of c-Myc signaling. The above-mentioned findings confirmed PF and PT as promising complementary resources to the official pharmacopoeial species. This work provides a critical chemical and pharmacological foundation for their quality standardization and potential therapeutic application in hemostasis and liver cancer management.
Perturbation of the quaternary state of insulin aspart formulation after prolonged storage in a closed-vial, real-world setting.
Kawale A, Malmodin D, Forsander G … +2 more , Karlsson BG, Nord AB
J Pharm Biomed Anal · 2026 Sep · PMID 42030705 · Publisher ↗
People with diabetes from many developing countries find it challenging to follow manufacturers' guidelines regarding strict storage conditions for insulin. What happens to insulin formulations exposed to real-world scen...
People with diabetes from many developing countries find it challenging to follow manufacturers' guidelines regarding strict storage conditions for insulin. What happens to insulin formulations exposed to real-world scenarios is important to understand before adjusting the current recommendations to decrease wastage and increase global accessibility. Upon investigating the effect on the potency of insulin formulations lacking refrigeration during the summer in India, we observed a subtle (≤ 5%) decline in the relative potency over the four months in our previous study. In this report, we present the biophysical characterization of the 'rapid-acting' analogue insulin aspart using Nuclear Magnetic Resonance (NMR), Thioflavin T (ThT) fluorescence assay, Size Exclusion Chromatography coupled with Multi-Angle Light Scattering (SEC-MALS), and Native PAGE to decipher the cause behind this subtle potency decline upon prolonged storage. We report that insulin aspart undergoes a time-dependent gradual establishment of insulin quaternary structure equilibrium, without any detectable formation of fibrils upon prolonged storage at elevated temperature. This crucial information about temperature-associated changes in insulin aspart might aid in better preparation and handling of insulin in developing countries.
An ultrasensitive chemiluminescence immunoassay for the detection of thyroid stimulating hormone based on antibody charge distribution-guided directional conjugation on magnetic beads.
Wan Z, Lu Z, Jiang P … +1 more , Yang H
J Pharm Biomed Anal · 2026 Sep · PMID 42024958 · Publisher ↗
To address the insufficient sensitivity (0.01 μIU/mL) of the currently widely used "third-generation" thyroid-stimulating hormone (TSH) detection reagent, we developed a "fourth-generation" ultrasensitive chemiluminescen...
To address the insufficient sensitivity (0.01 μIU/mL) of the currently widely used "third-generation" thyroid-stimulating hormone (TSH) detection reagent, we developed a "fourth-generation" ultrasensitive chemiluminescence immunoassay (CLIA) kit using oriented antibody conjugation technology by finely tailoring the surface charge distribution according to the charge heterogeneity between the Fab and Fc domains. Furthermore, we implemented a design of experiments (DOE) optimization with three variables at two levels for antibody conjugation, varying (1) the pH value, (2) the temperature, and (3) the antibody dosage, resulting in an optimized protocol that in favor of oriented antibody conjugation to magnetic beads. The optimized TSH-CLIA kit achieved an exceptional sensitivity of 0.0017 μIU/mL and the coefficient of variation (CV) of within-run, between-run, between day and within-laboratory precision were all lower than 10%. Method comparisons demonstrated a reasonable agreement (r > 0.99) with both Roche-ECL and Mindray-CLIA, and the Bland-Altman analysis showed that the limits of agreement were -12.6% and 12.4%, -14.3% and 12.5%, respectively. Certified reference material testing also demonstrated excellent accuracy with average relative bias all below 10%. Comparative measurements of clinical serum samples demonstrated high sensitivity (99.32%) and negative predictive value (95.12%), and a significant higher detection rate (79.5%) than that with Roche-ECL was achieved in low-concentration samples (< 0.27 μIU/mL) measurements. Crucially, our kit could accurately monitor the concentration fluctuations of subclinical hyperthyroidism and post-thyroidectomy patients 2 weeks earlier than conventional kit, which provides more timely information for the clinical dynamic monitoring of changes in hormone levels.
Investigating the pharmacokinetics and conjugate metabolism of potential hepatotoxic prenylflavonoids in Epimedium extract using LC-MS/MS.
Peng X, Zhang L, Gao S … +3 more , Zhang Q, Yang S, Li Y
J Pharm Biomed Anal · 2026 Sep · PMID 42019091 · Publisher ↗
This study aimed to investigate the pharmacokinetics and conjugate metabolism of four potentially hepatotoxic prenylflavonoids-sagittatoside A, icariside I, baohuoside I, and icaritin-from Epimedium extract. A rapid and...
This study aimed to investigate the pharmacokinetics and conjugate metabolism of four potentially hepatotoxic prenylflavonoids-sagittatoside A, icariside I, baohuoside I, and icaritin-from Epimedium extract. A rapid and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for their simultaneous quantification in rat plasma. Following oral administration of Epimedium extract at three dose levels, the plasma concentration-time curves of the four prototype flavonoids were characterized, revealing distinct pharmacokinetic profiles. Notably, icaritin exhibited a markedly delayed T and a prolonged elimination half-life, consistent with enterohepatic circulation. Subsequent enzymatic hydrolysis with β-glucuronidase significantly increased the measured concentrations of all compounds, indicating extensive in vivo glucuronidation. The fold-increase in systemic exposure (AUC) post-hydrolysis varied considerably among the flavonoids and showed a dose-dependent decrease, suggesting possible saturable conjugation metabolism. This study elucidates the differential pharmacokinetic profiles of four key prenylflavonoids from Epimedium extract. The results identify icaritin as the component with the highest systemic exposure and greatest potential for accumulation, suggesting it may be a candidate contributor to Epimedium-associated hepatotoxicity. These findings provide a pharmacokinetic foundation for future toxicological investigations.
Identification of anticancer and cardioprotective quality markers in Chuanxiong Rhizoma using a bioassay driven effect-constituent index approach.
Yang J, Liu X, Fan L … +3 more , Qi S, Li C, Li G
J Pharm Biomed Anal · 2026 Sep · PMID 42013688 · Publisher ↗
Ligusticum Chuanxiong (Chuanxiong Rhizoma) is used in Traditional Chinese medicine (TCM) and has cardioprotective effects. Trastuzumab improves outcomes in HER2-positive breast cancer, but acquired resistance and cardiot...
Ligusticum Chuanxiong (Chuanxiong Rhizoma) is used in Traditional Chinese medicine (TCM) and has cardioprotective effects. Trastuzumab improves outcomes in HER2-positive breast cancer, but acquired resistance and cardiotoxicity limit its utility. Current quality-control methods rarely integrate composition with functional efficacy, hindering rational standardization. We developed an efficacy-oriented quality-control strategy that couples HPLC profiling with in vitro bioassays. HPLC profiling of 12 commercial batches identified ten common constituents: tetramethylpyrazine, chlorogenic acid, ferulic acid, senkyunolide I, senkyunolide H, 6″-feruloylspinosin, senkyunolide A, n-butylbenzene, ligustilide, and butenylbenzene. All constituents were evaluated by CCK-8 assay to identify those with both cytotoxic activity against a trastuzumab-resistant HER2-positive breast cancer cell line and protective effects against trastuzumab-induced cardiomyocyte injury. We constructed two Effect-Constituent Indexes (ECI for cytotoxicity; ECI for cardioprotection) by weighting abundances by measured bioactivities. Both indices correlated with experimentally determined potency (ECI vs 1/IC: r = 0.727, **P < 0.01; ECI vs 1/EC: r = 0.592, *P < 0.05) and discriminated batches better than single markers. Batch S10 exhibited the strongest dual efficacy (IC = 0.6553 mg/mL; EC = 0.00288 mg/mL). Molecular docking indicated that bioactive constituents may modulate ferroptosis via interactions with SLC7A11 and FSP1. The integrated ECI framework offers an efficacy-driven quality control approach for Chuanxiong Rhizoma and supports its dual application to enhance antitumor activity while mitigating trastuzumab-induced cardiotoxicity.
Development and validation of an UHPLC-MS/MS method for simultaneous quantification of Tazobactam, Meropenem, Vancomycin, Linezolid and Piperacillin in human plasma: Application in critically ill patients.
Lucchetti J, Fracasso C, Cesana D … +3 more , Dore F, Finazzi S, Gobbi M
J Pharm Biomed Anal · 2026 Sep · PMID 42013687 · Publisher ↗
Antibiotic treatment for severe infections in critically ill patients might be challenging. The pathophysiological changes occurring in these patients can alter the pharmacokinetic profiles of antibiotics, resulting in i...
Antibiotic treatment for severe infections in critically ill patients might be challenging. The pathophysiological changes occurring in these patients can alter the pharmacokinetic profiles of antibiotics, resulting in ineffective or incorrect treatments, with potentially dangerous consequences. In this scenario, therapeutic drug monitoring is crucial for timely adjusting therapy and improving antibiotic effectiveness. In this study, we developed and validated an ultrahigh-performance liquid chromatography coupled with tandem mass spectrometry method for simultaneous quantification of five antibiotics - Tazobactam, Meropenem, Vancomycin, Linezolid and Piperacillin - in human plasma. Detection was achieved using a triple-quadrupole mass spectrometer in multiple reaction monitoring mode, with chromatographic separation via a binary gradient elution in 10 min. Method validation following ICH M10 guidelines confirmed that a single-step protein precipitation efficiently extracted all five drugs, ensuring accurate and precise quantification without matrix interference. The method was then successfully applied to measure antibiotics concentrations in plasma from 64 critically ill patients admitted in intensive care unit and treated with one or more of these drugs simultaneously.
Deep eutectic solvent-assisted magnetic nanoparticle extraction of curdione from Curcuma wenyujin for analytical and bioactivity evaluation.
Yuan H, Li J, Chen S … +6 more , Huang H, Jia X, Chen J, Huang X, Zhao X, Wang X
J Pharm Biomed Anal · 2026 Sep · PMID 42013634 · Publisher ↗
To improve the extraction efficiency of hydrophobic bioactive compounds and reduce organic solvent consumption, a deep eutectic solvent-assisted magnetic nanoparticle (DES-MNPs) extraction method was developed for the de...
To improve the extraction efficiency of hydrophobic bioactive compounds and reduce organic solvent consumption, a deep eutectic solvent-assisted magnetic nanoparticle (DES-MNPs) extraction method was developed for the determination of curdione in Curcuma wenyujin. Ethylene glycol/choline chloride (EG/ChCl) was employed as a hydrogen-bond-rich extraction medium, while dispersed magnetic nanoparticles were introduced to enhance mass transfer and enable rapid magnetic separation. Key extraction parameters were optimized using single-factor experiments combined with a Box-Behnken response surface design. Under the optimized conditions, the curdione concentration reached 0.125 mg/mL, representing a slightly higher yield (11.6%) compared with conventional ultrasound-assisted extraction using 70% ethanol. The improved extraction performance was attributed to the favorable solvation capability of the DES and the enhanced dispersion and mass transfer provided by the magnetic nanoparticles. The applicability of the developed method was further demonstrated through the bioactivity evaluation of the obtained extract, including antibacterial, anti-inflammatory, and antioxidant activities. Overall, this study presents an efficient and environmentally benign sample preparation strategy for the extraction and analysis of hydrophobic natural products from complex plant matrices.
Development and validation of a rapid UPLC-MS/MS method for quantifying bevacizumab in human plasma and application in Chinese cancer patients.
Yang H, Song W, Yang M … +7 more , Yang X, Li R, Cao H, Zhao X, Liu R, Lu Q, Wang L
J Pharm Biomed Anal · 2026 Sep · PMID 42013633 · Publisher ↗
Bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor, is widely used in the treatment of various cancers. Despite its efficacy, the drug exhibits significant interindividual variability in phar...
Bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor, is widely used in the treatment of various cancers. Despite its efficacy, the drug exhibits significant interindividual variability in pharmacokinetics and clinical response. This study aimed to develop and validate a rapid, sensitive, and cost-effective ultra-performance liquid chromatography-tandem mass spectrometry method for quantifying bevacizumab in human plasma. Bevacizumab was quantified using the surrogate peptide, FTFSLDTSK. The IgG-based drug, infliximab was used as internal standard. The method was validated for specificity, linearity, precision, accuracy, recovery, matrix effect, stability, and applied in 48 plasma samples from Chinese patients with cancers. The method showed a linear range of 1-200 mg/L, and validation parameters met the required standard criteria. A 14-fold inter-individual variability in bevacizumab trough concentrations (ranging from 10.31 to 143.07 mg/L) was observed, with differences across cancer types. This method provides a simple and rapid approach for bevacizumab quantification and may support individualized dosing strategies.
A sustainable optical nanosensor based on biogenic mesoporous silica and a chromophore for ultra-trace Fe³ ⁺ determination in environmental and pharmaceutical samples.
Subaihi A, Alharbi A, Hussein WM … +4 more , El-Sonbati AZ, Kamel RM, Baset MA, Shahat A
J Pharm Biomed Anal · 2026 Sep · PMID 41999702 · Publisher ↗
In this work, a highly responsive chemo-sensor was designed for the trace determination of Fe³ ⁺ ions in industrial wastewater. The sensing platform is constructed by anchoring the 3-allyl-5-[(4-nitrophenylazo)-2-thioxot...
In this work, a highly responsive chemo-sensor was designed for the trace determination of Fe³ ⁺ ions in industrial wastewater. The sensing platform is constructed by anchoring the 3-allyl-5-[(4-nitrophenylazo)-2-thioxothiazolidin-4-one (HL5) ligand onto mesoporous nanosilica prepared through a green, rice-husk-derived synthesis route. The resulting material provides a well-defined porous framework that enhances ligand loading and facilitates rapid metal-ion diffusion. The structural, morphological, and surface characteristics of both the nano silica support and the final HL5 sensor were thoroughly investigated using Fourier Transform Infrared Spectroscopy (FTIR), Scanning Electron Microscope (SEM), Transmission Electron Microscope (TEM), Brunauer-Emmett-Teller (BET) analysis, and X‑ray Diffractometry (XRD). Key spectrophotometric variables, including pH, contact time, sensitivity, and selectivity, were systematically optimized to achieve maximum analytical performance. Under the optimized conditions, the sensor reliably detected Fe³ ⁺ at ultra-trace levels. Method validation following ICH guidelines confirmed excellent linearity, precision, and quantification capability, with a detection limit of 12.95 µg/L. The HL5-modified nanosilica also demonstrated notable regeneration potential; after treatment with 0.1 M Ethylenediaminetetraacetic acid (EDTA), the sensor retained its functionality for up to eight consecutive cycles. Application studies showed that the developed system performs effectively in diverse matrices, including industrial effluents and pharmaceutical iron formulations. Overall, the proposed chemo-sensor offers a selective, sensitive, and reusable platform suitable for real-world iron monitoring.
Validation of a quantitative analysis method for tryptophan metabolites in asthmatic mice and bacteria using GC-MS/MS.
Xu W, Shang M, Luo Z … +5 more , Ji X, Shan Y, Chen Q, Shan J, Zhang Z
J Pharm Biomed Anal · 2026 Sep · PMID 41990598 · Publisher ↗
This study established a gas chromatography-tandem mass spectrometry (GC-MS/MS) method for the simultaneous quantification of 25 tryptophan (TRP) metabolites encompassing the kynurenine pathway, serotonin pathway, and in...
This study established a gas chromatography-tandem mass spectrometry (GC-MS/MS) method for the simultaneous quantification of 25 tryptophan (TRP) metabolites encompassing the kynurenine pathway, serotonin pathway, and indole pathway. The method was systematically validated in terms of precision and accuracy, demonstrating robust reliability. Application of this method to bacterial cultures as well as serum and lung tissues from asthmatic mice revealed significant alterations in TRP metabolic profiles. Owing to its high throughput and sensitivity, this method is well suited for the analysis of TRP metabolites in complex biological matrices and provides a robust platform for comprehensive profiling of TRP metabolites in complex biological matrices, facilitating studies of TRP metabolism in asthma.
UHPLC-Orbitrap-HRMS-based metabolite identification and profiling of methylophiopogonone A, A bioactive constituent from Ophiopogon japonicus.
Zhu Y, Zhang P, Cao M … +1 more , Ma Z
J Pharm Biomed Anal · 2026 Sep · PMID 41990597 · Publisher ↗
Methylophiopogonone A (MON-A), an anti-inflammatory constituent of Ophiopogon japonicus, demonstrates therapeutic potential for liver fibrosis in patients with chronic hepatitis B and SARS-CoV-2 infection. This study aim...
Methylophiopogonone A (MON-A), an anti-inflammatory constituent of Ophiopogon japonicus, demonstrates therapeutic potential for liver fibrosis in patients with chronic hepatitis B and SARS-CoV-2 infection. This study aimed to investigate its metabolic profile using liver microsomes and cryopreserved hepatocytes from humans and three preclinical species (rat, dog, and monkey). MON-A was incubated separately with each system, and the samples were analyzed by ultra-high-performance liquid chromatography coupled with quadrupole/Orbitrap high-resolution mass spectrometry (UHPLC-Orbitrap-HRMS) in positive electrospray ionization mode. Data were processed using Compound Discoverer software with mass defect filtering. Metabolite structures were characterized based on accurate mass and MS fragment ions. A total of 14 metabolites were identified. The primary metabolic pathways included hydroxylation, oxidative methylenedioxyphenyl (MDP) ring-opening, oxidation, and glucuronidation. M11 (a glucuronide conjugate) was the most abundant metabolite across all species. Additionally, four glutathione (GSH) conjugates were detected, indicating the formation of reactive metabolites, notably ortho-quinone and quinone methide species. The formation of quinone methide species revealed that C-C double bond is essential for the metabolic activation of the A-ring. This systematic study clarifies the metabolic fate of MON-A, providing important insights into its biotransformation pathways and potential for reactive metabolite formation. The results establish a foundation for evaluating both the therapeutic efficacy and safety profile of this anti-inflammatory candidate during preclinical development.
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