Latest ArticlesTo analyze the bioequivalence and safety of the test and reference formulations of erlotinib hydrochloride tablets in healthy Chinese subjects under fasting conditions following a single oral dose.
The study was conducted as a randomized, open-label, two-period crossover trial. A total of 60 healthy subjects were assigned to two sequences by randomization. Under fasting conditions, subjects received a single 150 mg oral dose of either the test or reference formulation, with a 12-day washout period between doses. The plasma concentrations of erlotinib were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS), and the pharmacokinetic parameters were calculated for bioequivalence evaluation using Phoenix WinNonlin software (version 8.3).
After a single oral administration of the test or reference formulation under fasting conditions, the main pharmacokinetic parameters of erlotinib hydrochloride were as follows: maximum concentration (Cmax) was (1 649.48±567.44) and (1 548.15±529.59) ng·mL-1, AUC0-last were (28 830.12±11 507.57) and (29 396.47±11 121.61) h·ng·mL-1, AUC0-inf were (30 759.13±13 789.60) and (31 132.78±12 912.53) h·ng·mL-1. The 90% confidence intervals for the geometric mean ratios of Cmax, AUC0-last, and AUC0-inf for the two formulations were 92.44%-117.31%, 87.65%-103.90% and 87.66%-104.37%, respectively, all of which were within the bioequivalence acceptance range of 80.00%-125.00%. No serious adverse events, suspected unexpected serious adverse reactions, or adverse events leading to withdrawal occurred during the trial.
Under fasting conditions, the test erlotinib hydrochloride tablets were bioequivalent to the reference listed drug Tarceva® in healthy Chinese subjects and the safety profile was favorable.
To develop and validate a liquid chromatography tandem mass spectrometry (LC-MS/MS) method for determining the concentration of posaconazole in dried blood spot (DBS) samples, providing a feasible reference for the application of the dried blood spot method and the clinical practice of posaconazole therapeutic drug monitoring (TDM).
DBS samples were obtained by dropping whole blood samples containing posaconazole onto Whatman 903® cards and drying them. The sample processing procedure involved cutting out a round hole with a diameter of 3 mm to obtain the analytical sample. The sample was extracted by adding 0.2% formic acid-50% acetonitrile (containing an internal standard of 0.50 μg·ml-1), followed by sonication and centrifugation. The supernatant was directly injected for detection. LC-MS/MS was used for determination. The Phonomenex Kinetex XB-C18 column was selected as the chromatographic column, and gradient elution was used for separation. The mass spectrometry detection mode was positive ion multiple reaction monitoring. The monitored ion pairs for the analyte posaconazole and the internal standard D5-posaconazole were 701.3→614.4 and 705.3→618.4, respectively. Full method validation was conducted in accordance with ICH Guideline M10 (Bioanalytical Method Validation and Study Sample Analysis), covering selectivity, specificity, linearity, carryover, accuracy, precision, extraction recovery, matrix effect, analyte stability, together with DBS-specific validation parameters including hematocrit (Hct) impact, spotting volume effect and spot homogeneity. In addition, the developed DBS method was applied to the detection of clinical TDM samples of posaconazole and compared with the plasma method, and the consistency of the two methods was evaluated.
The LC-MS/MS method for the determination of posaconazole in DBS had good selectivity and linearity (0.10-10.00 μg·ml-1), without the influence of cross-talk and carry-over. The recovery rate of the analyte during the sample processing was in the range of 70.67%-75.66%. The intra-batch accuracy and precision were in the ranges of -12.18%--0.86% and 3.05%-8.75%, respectively, and the inter-batch accuracy and precision were in the ranges of -4.21%-3.49% and 8.57%-12.21%, respectively. For the matrix effect tested with six blank whole blood samples from different sources, the accuracy was within ±15% and the precision was all <15%. The stability results showed that posaconazole was stable for at least 3, 3, 14, 30, and 90 days at room temperature (20-25 ℃), 37 ℃, 4 ℃ -20 ℃, and -70 ℃ in DBS samples, respectively. The results of Bland-Altman and Passing-Bablok analyses of 78 clinically verified samples showed that there was a good correlation between the determination results of posaconazole in dried blood spots (DBS) and plasma. However, there was a significant deviation (P<0.001). The determination results in DBS were lower than those in plasma (average difference=0.33 μg·ml-1), and this was more significant in cases with low hematocrit (Hct).
A straightforward and practical LC-MS/MS method was successfully developed and fully validated for posaconazole quantitation in DBS samples. This method requires a minimal blood volume (minimum 10 μL whole blood), features a short analytical runtime (2.00 min per injection) and facilitates streamlined laboratory operation with robust practicability, which can serve as a convenient alternative analytical strategy for routine clinical TDM of posaconazole.
To establish a high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) method for simultaneous determination of calcitonin salmon in human plasma.
Precipitate plasma samples using organic reagents, then centrifuge and collect the supernatant, proceed with concentration, reconstitution, and sample injection, and a phenomenex Jupiter® C4-300A column (2.1 mm×50.0 mm, 5.0 μm) was used for chromatographic separation. The mobile phase was 0.1% formic acid water (phase A) -0.1% formic acid acetonitrile (phase B); gradient elution with a flow rate of 0.50 mL·min-1, column temperature 50 ℃, injection volume 20 μL. A custom-labeled isotopic compound was used as the internal standard, scanning was carried out by means of multi reaction monitoring (MRM) in the positive ionization mode with an electric spray ionization source(ESI). Examine the specificity, standard curve, lower limit of quantification (LLOQ), precision, accuracy, recovery rate, matrix effect, and stability of the method.
The method showed a good specificity results of the method, and there is no interference between the analyte and the internal standard. The linear range of the standard curves for the tested substances was 2.00、4.00、10.00、50.00、100.00、200.00、360.00、400.00 pg·mL-1, The standard curve was y=2.98×10-2x+5.30×10-3 (R2=0.997 4) and the lower limit of quantification(LLOQ) is 2.00 pg·mL-1. The intra-day and inter day relative standard deviation (RSD) were both less than 15%, extraction recovery rates ranging from 60.13% to 75.39% (RSD<15%), and matrix effects ranging from 97.45% to 109.72% (RSD<10%). The stability of the matrix samples was verified by placing them at room temperature for 24 hours, repeatedly freezing and thawing at -20 ℃ and -70 ℃ for 5 times, freezing at -20 ℃ and -70 ℃ for 49 days, and placing the processed samples in an automatic sampler for 333 hours, with accuracy ranging from 97.03% to 108.64%, all stable.
The established HPLC-MS/MS method is simple, rapid, highly sensitive, and specific, and can be used for the detection of plasma samples in pharmacokinetic studies.
To analyze the adverse drug reactions (ADRs) of 0.01% atropine sulfate eye drops in myopia control among children and adolescents, providing safety evidence for its clinical application.
Retrospective analysis of ADR data from pediatric and adolescent patients using the 0.01% atropine sulfate eye drops (hospital-prepared formulation) in our institution from January 2022 to December 2024.
A total of 51 ADR cases were collected, with an incidence rate of 0.29%. Visual disorders were the most frequent (54.71%), primarily manifesting as eye pain, blurred vision, and photophobia; followed by skin and subcutaneous tissue disorders (11.76%), mainly presenting as rash; and nervous system disorders (9.80%), including dizzinessand headache. Newly reported ADRs accounted for 35 cases (68.63% of total reports). All ADRs were mild or moderate, with no severe cases observed.
0.01% atropine sulfate eye drops show favorable short-term safety and a low incidence of adverse drug reactions in myopia control among children and adolescents. As a real-world pharmacovigilance data report, this study provides certain cautions for the clinical use of 0.01% atropine sulfate eye drops; however, its long-term safety requires further investigation and validation.
To evaluate the effectiveness of the plan-do-check-act (PDCA) cycle combined with a drug use pathway in managing the rational use of proton pump inhibitors (PPIs) hospital-wide.
Based on evidence-based medicine, PPI treatment and prophylactic medication pathways were established and implemented through the PDCA cycle. The changes in PPI usage rationality, quarterly average sales amount and its proportion of total drug consumption, medication frequency (DDDs), usage intensity (AUD), medication structure and intravenous usage rate in hospitalized patients were compared before implementation (fourth quarter of 2023) and after implementation (first to third quarters of 2024).
After the implementation of medication pathways, the rationality of PPI use across the hospital significantly improved. The prescription compliance rate increased from 95.17% (571 prescription/600 prescription) to 98.50% (589 prescription /600 prescription), and the order compliance rate rose from 93.33% (140 prescription /150 prescription) to 97.33% (149 prescription /150 prescription). Costs also decreased, with quarterly consumption dropping from 37.82 to 25.98 million yuan, with a reduction of 31.31%, and the cost proportion declining from 0.97% to 0.80%, with a decrease of 17.53%. The reduction in usage intensity was greater than the total volume, with AUD decreasing from 208.48 to 126.28 (with a 39.43% reduction) and DDDs dropping from 153 071.29 to 103 490.17 (with a 32.39% reduction). The medication structure continued to optimize, with the proportion of high-cost PPIs decreasing from 52.35% to 38.28% (with a 26.88% reduction), while the proportion of centralized procurement/essential drugs increased from 40.99% to 42.42% (with a 3.45% rise). The intravenous usage rate declined from 15.51% to 14.67% (with a 5.41% reduction). The intervention effectively achieved the goals of cost control, quality improvement, and compliance.
The PDCA cycle can effectively promote the implementation of drug use pathways and enhance the level of rational drug use.
Propofol is one of the most widely used intravenous general anesthetics in clinical practice, mainly due to its rapid onset of action, short half-life period, and high clearance rate. However, propofol is associated with a variety of adverse drug reactions, such as injection site pain, hypotension, respiratory depression, hyperlipidemia, allergies, and propofol infusion syndrome. As a water-soluble prodrug of propofol, fospropofol disodium possesses unique formulation advantages and controllable pharmacological properties, and has been gradually applied in the field of clinical anesthesia. This article aims to systematically review the pharmacological characteristics, clinical research progress, advantages and limitations of fospropofol disodium, and prospect its future application prospects in clinical anesthesia.
Sarcopenia-osteoporosis is an age-related syndrome caused by the coexistence of osteoporosis and sarcopenia, and it poses a serious threat to the health of the elderly population. The mitogen-activated protein kinases (MAPKs) signalling pathways, including extracellular signal-regulated kinase 1/2 (ERK1/2), p38 MAPK and c-Jun N-terminal kinase (JNK), regulate the proliferation, differentiation and apoptosis of skeletal muscle and bone tissue, and play a significant role in the development and progression of sarcopenia-osteoporosis. In recent years, various traditional Chinese medicine (TCM) constituents have demonstrated experimental value in modulating the MAPKs signalling pathway and influencing processes related to osteogenesis or muscle atrophy. This article reviews the regulatory effects of the MAPKs signalling pathway in osteogenesis and myogenesis, and summarises research progress on the use of various TCM monomers to intervene in sarcopenia-osteoporosis via this pathway, with the aim of providing new theoretical foundations and therapeutic strategies for the prevention and treatment of sarcopenia-osteoporosis.
Diabetic kidney disease (DKD), a common and severe complication of both type 1 and type 2 diabetes, has become the leading cause of chronic kidney disease and end-stage renal disease. Current clinical treatments for DKD mainly focus on glycemic control and renal function protection, but existing strategies still fail to effectively halt the progressive decline of renal function. Patients often eventually progress to renal failure accompanied by cardiovascular complications. The complexity of the pathophysiological mechanisms of DKD determines the limitations of single-target interventions and highlights the necessity of multi-pathway synergistic therapy. Studies have shown that traditional Chinese medicine monomers can exert effects through multiple pathways: they not only regulate disordered glucose and lipid metabolism and alleviate oxidative stress and mitochondrial dysfunction, but also inhibit inflammatory responses, modulate autophagy levels, antagonize apoptosis, and regulate the renin-angiotensin-aldosterone system. This article systematically reviews the recent research progress of traditional Chinese medicine monomers in the intervention of DKD, analyzes the current limitations and deficiencies, and prospects future development directions, so as to provide theoretical support for the research and development of novel therapeutic strategies for DKD.
Oleanolic acid (OA), a naturally occurring pentacyclic triterpenoid compound, is widely distributed in plants such as hawthorn and lycium barbarum. It possesses various biological activities including anti-inflammation, antioxidation, anti-tumor and anti-aging. In recent years, more and more studies have shown that OA can delay the aging process through multiple pathways, ①regulating oxidative stress response by activating the nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling 1 pathway to enhance the activity of antioxidant enzymes, such as superoxide dismutase (SOD) and catalase (CAT), and reduce reactive oxygen species (ROS) accumulation; ②inhibiting inflammatory-related pathways, such as nuclear factor-kappa B (NF-κB) and NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, to lower the levels of pro-inflammatory factors, such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) ; ③activating the silent mating type information regulation 2 homolog (SIRT1) / adenosine monophosphate-activated protein kinase (AMPK) pathway to improve mitochondrial function, promote autophagy, and delay cellular aging; ④regulating the senescence-associated secretory phenotype (SASP) and inhibiting the tumor protein p53 (p53)/cyclin-dependent kinase inhibitor 1A (p21) signaling pathway to reduce cell cycle arrest. This article reviews the multi-target anti-aging mechanism of OA and explores its potential application value, aiming to provide theoretical basis and new ideas for anti-aging research.
Advanced therapy medicinal products (ATMPs), as a cutting-edge frontier in the current biomedical sector, hold enormous potential to address unmet clinical medical needs. Nevertheless, such products are confronted with multiple challenges including high technical complexity, distinctive research and development risks and substantial investment costs. Their accurate classification and scientific regulation are critical to advancing the standardized development of the industry. Over years of practical experience, the European Medicines Agency (EMA) has established a robust legal and regulatory system, accompanied by a series of issued guidelines, thus forming a relatively mature regulatory framework. Furthermore, relying on the Committee for Advanced Therapies (CAT), the EMA has developed a comprehensive mechanism for the classification, designation, and communication of ATMPs, which serves as an important reference for the global regulation of ATMPs. This paper systematically elaborates on the classification criteria and designation procedures of ATMPs formulated by the EMA, and introduces its practical communication practices, including scientific advice and innovation task force briefings. This paper provides insights and references for improving China’s ATMP classification management system, optimizing the evaluation and communication mechanism, and constructing a scientific and efficient regulatory framework.
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