OBJECTIVE To establish a predictive model for drug-induced liver injury (DILI) of tigecycline (TGC) to enable early recognition and management of high-risk patients. METHODS A retrospective study was performed on intensive care unit inpatients receiving TGC treatment at the first affiliated hospital of Zhengzhou university between January 2023 and March 2024. Demographics, medical history, admission characteristics, and treatment data were collected. Lasso-logistic regression analysis was used to identify risk factors for TGC-induced DILI. A nomogram was constructed based on these factors, and its predictive performance was assessed. RESULTS A total of 242 patients were enrolled, including 78 in the DILI group and 164 in the non-DILI group. The DILI group had higher proportions of females, age ≥60 years, alcohol consumption, acute physiology and chronic health evaluation Ⅱ(APACHE Ⅱ) scores ≥21, TGC treatment durations ≥14 d, TGC overdosing, and concomitant use of ≥3 d compared with the non-DILI group (P<0.05). Logistic regression analysis indicated that female, age≥60 years, APACHE Ⅱ score ≥21, TGC treatment duration ≥14 d, TGC overdosing, and concomitant use of≥3 medications were independent risk factors for TGC-induced DILI (P<0.05). The area under the curve (AUC) of the nomogram was 0.870 (95%CI: 0.795-0.952). Calibration curve analysis suggested good agreement between model predictions and observations, and the decision curve showed that the patients could obtain clinical benefit within the threshold range of 10%-95%. CONCLUSION Gender, age, APACHE Ⅱ score, TGC duration, TGC overdose and concomitant medication are risk factors of TGC-induced DILI, and the nomogram based on these variables has good clinical performance.

OBJECTIVE To establish a liquid chromatography-tandem mass spectrometry(LC-MS/MS) method for the simultaneous determination of the concentrations of verapamil and norverapamil in human breast milk and apply it in clinical practice. METHODS Milk samples(100 μL) were precipitated with 300 μL of methanol containing internal standard(5 ng·mL^-1 verapamil-d₃), and the supernatant was taken for analysis after vortexing and centrifugation. The chromatographic separation was performed on a Waters ACQUITY BEH C₁₈ column with gradient elution at 0.4 mL·min^-1, where mobile phases A and B were 0.1% formic acid-10 mmol·L^-1 ammonium acetate-water and methanol, respectively. The injection volume was 2 μL, and the analysis time was 4 min. The detection of the analytes was performed by electrospray ionization in positive mode by multiple reaction monitoring with the transition of m/z 455.3→165.2(verapamil), m/z 441.5→165.3(norverapamil) and m/z 458.3→165.0(verapamil-d₃). The established LC-MS/MS method was validated, and the method was used to determine the drug concentrations in breast milk of lactating patients. RESULTS The calibration curves for verapamil and norverapamil exhibited good linearity within the concentration range of 0.5 to 100 ng·mL^-1 (r=0.999). The intra-assay and inter-assay accuracies were both within ±15% of the labeled values, and the relative standard deviations were less than 15%. The extraction recovery, matrix effect, and stability all met the acceptance criteria for bioanalytical method validation. This analytical method was effectively employed to quantify drug concentrations in the breast milk of a lactating patient. The verapamil concentration in the breast milk of the patient ranged from 1.80 ng·mL^-1 to 10.73 ng·mL^-1, while norverapamil concentrations varied from 2.15 ng·mL^-1 to 5.15 ng·mL^-1. The relative infant dose of verapamil in this patient was approximately 0.15%. CONCLUSION The established method is simple, rapid, and sensitive. It is suitable for monitoring drug concentrations in clinical milk and can provide reference for safe drug use during lactation.

OBJECTIVE To develop and verify two methods for the detection of size distribution of residual Vero cell DNA in the bulk of vaccine. METHODS Based on capillary electrophoresis and microfluidic chip-based electrophoresis, a method for separation and detection of residual Vero cell DNA fragments in different size which have been purified and fluorescent-labelled was established. The developed method was verified for specificity, accuracy, repeatability, sensitivity, and used for detection of size distribution of residual Vero cell DNA fragments in the bulk of two different vaccines. RESULTS Thirteen DNA fragments of different size were separated at baseline level. The relative deviation in retention time between the control product with 200, 500, 1 000 bp DNA and the reference product were lower than 0.5%. The average relative deviations of retention time by 6 times detection of 13 DNA fragments were 0.72% and 0.11%, respectively. The LODs were 1.5 and 0.1 pg·μL^-1, respectively. The blank control showed no influence on the test. The result of the sample added with standard DNA fragments was in accordance with the theoretical expectation. No peak was detected in one kind of vaccine sample, and the other one showed two groups of peaks representing different size. CONCLUSION The developed method has good specificity and high sensitivity. It is convenient and rapid, which is suitable for the determination of size distribution of residual DNA fragments in the bulk of vaccine.

OBJECTIVE To develop and validate an HPLC analytical method for finerenone, based on the concept of analytical quality by design (AQbD). METHODS LC-MS was used to identify the impurity fractions of finerenone API, and then the HPLC chromatographic conditions of finerenone were screened and optimized by analytical factorial design (2^5-1), which examined several factors, such as the acetonitrile proportion at the beginning of the elution gradient, the acetonitrile proportion at the end of the elution gradient, the elution time, the column temperature and the concentration of phosphoric acid aqueous solution, to evaluate the relationship between the critical method attributes (CMAs) and the critical method parameters (CMPs), and to generate the method operable design region (MODR), and finally perform methodological validation. RESULTS The effects of each CMPs on CMAs were analyzed, and the optimized chromatographic conditions from MODR were column temperature 45 ℃, 0.06% phosphoric acid water, gradient elution starting with 5% acetonitrile and ending with 45% acetonitrile, running for 16 min. The established finerenone analysis method had good precision, stability, linearity and sample recovery results. CONCLUSION The chromatographic conditions established based on the AQbD concept can achieve a good separation of finerenone from impurities, accurately evaluate the content of finerenone, and effectively control the quality of the drug.

OBJECTIVE To develop a new strategy for the value assignment of melting point reference standards based on optimized statistical methods, in order to enhance the accuracy and reliability of the assigned values. METHODS The development process included several key steps: structural confirmation, purity analysis, homogeneity evaluation, collaborative calibration of melting point, data preprocessing, factorial analysis, difference testing, equivalence testing, and robust statistical assignment. Using JMP software for statistical analysis, the process first involved removing outliers and conducted normality tests and homogeneity of variance tests on the melting point data. Subsequently, factorial analysis was employed to identify the main factors affecting the melting point. Each factor was then individually verified through difference testing. Equivalence testing was also conducted to determine whether the differences were within an acceptable range. Finally, based on the statistical results, the method and scope of robust statistical assignment were determined to value the melting point reference standards. RESULTS The reference materials and heating rates were identified as the main factors affecting the melting point. For each of the four model drugs, the calibration results of the same reference material were excluded because these results showed significant differences from the others and were not equivalent. The results from the remaining two reference materials and the two measurement methods were combined for statistical analysis, while the results from the two different heating rates were analyzed independently. CONCLUSION The accuracy of value assignment for melting point reference standards is improved through standardized experimental operations and optimized statistical methods, and the development process is systematically organized for the first time.

OBJECTIVE Analyze the key control points and risk points of the process, propose the key points of the review and inspection, based on the continuous encapsulation process of lipid nanoparticles. METHODS On the basis of analyzing the lipid components and coating process of marketed lipid nanoparticles, the similarities and differences in the realization methods, fluid properties, equipment material form, advantages and challenges were analyzed. The key control points, challenge points and risk points, and propose the key technical points of the process were analyzed. RESULTS The challenge and risk points of continuous encapsulation of lipid nanoparticles mainly focus on five aspects: process control model, selection of equipment and hybrid device, application and development of PAT technology, identification and control of disturbance, and disposal of abnormal events. Accordingly, six technical points that should be paid special attention to in the official review and inspection: process research and control strategy, equipment confirmation and plant facilities, process verification and continuous process confirmation, process analysis and control, cleaning verification and cross-pollution prevention and control, and data integrity. CONCLUSION In order to promote the industrialization scale application of new continuous manufacturing technology, review and inspection technical guide is very important. Drug regulatory agency should do more early researches together with the industry.

Ovarian cancer is a malignant tumor with a high mortality rate in women. PARP inhibitors (poly ADP-ribose polymerase inhibitors, PARPi), as one of the mainstays of maintenance therapy, can significantly improve the survival rate of patients; however, with the widespread use of PARPi, PARPi resistance has become an urgent problem in the treatment process. Current studies have found that metabolic reprogramming in the tumor microenvironment (TME) may affect chemoresistance in ovarian cancer through multiple mechanisms, but whether lipid metabolic reprogramming in the TME is involved in the formation of PARPi resistance is not clear. The aim of this paper is to explore the effect of lipid metabolism in TME on PARPi resistance in ovarian cancer in recent years and to analyze the possible link between it and PARPi resistance, with a view to providing new perspectives for further understanding the mechanism of PARPi resistance formation and searching for new therapeutic targets.

Long-acting injectable formulations are preferred over conventional formulations for the treatment of chronic diseases. An effort to build the relationship between an in-vivo property of a dosage form and an in-vitro response is often referred to as“in vitro-in vivo correlation” (IVIVC) analysis. This paper provides an overview of the classification, establishment and evaluation method of IVIVC. Due to long-acting injectable formulations' diverse nature, it is impractical to establish an universal IVIVC model in vitro, it is essential to develop individual IVIVC model in every study. Integrated knowledges of physicochemical, dosage form design and the interaction of the drug molecule with site of administration play important roles in the study of long-acting injectable formulations' IVIVC.

OBJECTIVE To investigate the secondary metabolites and hypolipidemic properties of Irpex lacteus. METHODS Compounds were isolated and purified using silica gel column chromatography, preparative high-performance liquid chromatography (Pre-HPLC), and other chromatographic techniques. Structural identification was performed through nuclear magnetic resonance (NMR), high-resolution mass spectrometry, infrared (IR), and ultraviolet (UV) spectroscopy. HepG2 cell model with high lipid was established to test the hypolipidemic activity. RESULTS Twelve compounds were isolated from Irpex lacteus and identified as (2α, 4β, 5β, 7β, 10α)-2, 5, 11-eudesmanetriol(1), 11, 12-epoxy-5, 6-secotremula-1, 6(13)-dien-5-12-olide(2), 8α, 10α-di-O-acetyl-lactarorufin A(3), (+)-(2S, 3R, 6S, 7S)-tremul-1(10)-ene-2, 12- diol(4), conocenolide A(5), irpexolactin G(6)、2, 2'-oxybis(1, 4-di-tert-butylbenzene) (7), 4'-hydroxy-5, 7-dimethoxy-6-(3-methyl-2-butenyl)- isoflavone(8), cyclo(Ile-Val) (9)、cyclo(L-Pro-L-Leu) (10), cyclo(Ile-Leu) (11), cyclo(Ile-lle) (12). The results of hypolipidemic activity showed that compounds 1-4, 8 and 9 had hypolipidemic activities, and the reduction effect of TG content in each dose group of compounds 1, 4 and the high and medium dose groups of compounds 2, 3 and 8 was better than that of the positive drug group. CONCLUSION Compounds 1-4, 7-12 are isolated from this strain for the first time. Compounds 1-4, 8 and 9 have good hypolipidemic effects.

OBJECTIVE To ensure the equivalence of the ancient and modern processes, and optimize the alcohol extractionprocess of Erxian Decoction(EXD), using standard relation andanalytic hierarchy process(AHP)-entropy weight method combinedwith Box-Behnken response surface method. METHODS Taking phellodendrine, mangiferin, ferulic acid, berberine, curculigoside, epmedin A1, epmedin A, epmedin B, epmedin C, icariin content, dry extract rate and fingerprint similarity as the key quality factors, taking ethanol concetration, solid-liquid ratio and extraction time as the key process parameters, the best extraction process was obtained by Box-Behnken response surface method. RESULTS The optimal conditions were 75% ethanol, 1∶14 solid-liquid ratio (g∶mL) and 62 min extraction time. The verified experimental results showed that the average comprehensive score was 86.64, and the relative standard deviation(RSD) was 1.02%. CONCLUSION The alcohol extraction process of EXD is optimized using standard relation combined with AHP-entropy weight method, the fitted model is significant, and the quality of the standard decoction is highly consistent, which provids a reference for the change of dosage form in the later stage.