To develop a gas chromatography-mass spectrometry (GC-MS) method for the determination of cyclohexane and potential genotoxic impurities (chlorocyclohexane and 1-cyclohexyl-1-phenylethanol) in trihexyphenidyl hydrochloride tablets.

The VF-WAXms capillary column (30 m × 0.25 mm, 1.00 μm) was used. High-purity helium was used as the carrier gas at a flow rate of 2.0 mL·min^-1, with a split ratio of 5∶1 and an injection volume of 2 μL. The mass spectrometer was equipped with an electron ionization (EI) source and operated in the selected ion monitoring (SIM) mode for detection.

The results showed that chlorocyclohexane, cyclohexanol, and 1-cyclohexyl-1-phenylethanol exhibited good linear relationships in the range of 25-250 ng·mL^-1, with detection limits (LOD) of 10.2, 10.0 and 9.8 ng·mL^-1, and quantification limits (LOQ) of 25.4, 25.0 and 24.5 ng·mL^-1, respectively. The average recovery rates (n = 6) were 98.93%, 102.93% and 99.97%, respectively.

The established method has good specificity and high sensitivity, and can serve as a reference for the quality control of trihexyphenidyl hydrochloride tablets.

Safe, effective, economical and appropriate rational drug use has become a crucial part of medical services. By summarizing the relevant theoretical research on pharmacoeconomic evaluation systems in recent years, this paper aims to propose a set of operable and easily promotable pharmacoeconomic evaluation paths.

This study mainly adopts literature research, expert consultation, comparative research and other methods to analyze the problems existing in the pharmacoeconomic evaluation system and put forward relevant suggestions.

Currently, there are issues with the relevant theoretical research on the pharmacoeconomic evaluation system in China, including an insufficiently systematic evaluation system, insufficient evaluation dimensions, and isolated data. It is necessary to further improve the evaluation system, enhance the theory of pharmacoeconomics evaluation, and strengthen the generalizability of research results.

This paper proposes a development path of the "policy guidance indicator optimization data-driven" trinity evaluation system, aiming to enrich and improve the pharmacoeconomic evaluation system, enhance the overall efficiency of pharmaceutical resource allocation, and provide useful references for deepening the reform of the medical and health system.

To establish a new pathway for the external validation of population pharmacokinetics (PPK) models based on real-world data, using aripiprazole in the treatment of schizophrenia as an example, and to explore a novel strategy for the clinical application of model-informed precision dosing (MIPD) and its feasibility.

A total of 101 patients with schizophrenia (1 178 blood drug concentration samples) were retrospectively enrolled at a class Ⅲ Grade A specialized hospital. Published PPK models of aripiprazole were identified by searching PubMed, Web of Science, and China National Knowledge Infrastructure (CNKI). Candidate models were evaluated using goodness-of-fit (R²) prediction error tests (PE, RPE%) to assess their predictive performance, and the model consistent with the characteristics of the blood concentration data was screened. Based on the selected PPK model, Monte Carlo simulation was performed to predict the steady-state plasma concentration of aripiprazole under different dosing regimens for individualized medication.

Three published PPK models of aripiprazole were included in this study. Goodness-of- fit and prediction error analyses showed that Model 3 had the best predictive performance. Based on Monte Carlo simulations with Model 3, plasma concentrations under 10 mg qd, 20 mg qd, and 30 mg qd regimens were ranked as IM > EM >UM in patients with the same body weight. For patients with the same CYP2D6 metabolic phenotype, plasma concentrations decreased with increasing body weight: 30 kg > 50 kg > 70 kg > 90 kg > 110 kg.

After validation with real-world data, the screened model with satisfactory predictive performance can be directly used in clinical practice to guide individualized medication and achieve model-informed precision dosing.

To characterize the pharmacokinetic characteristics of teicoplanin in patients with hypoalbuminemia, explore the target values of pharmacokinetic/pharmacodynamic (PK/PD) parameters, and develop individualized dosing regimens.

Clinical data of patients with hypoalbuminemia were retrospectively collected, and a population pharmacokinetic analysis was performed using a nonlinear mixed-effects model. Classification and regression tree (CART) analysis and survival analysis were used to explore and verify the impact of the target values of (PK/PD) parameters on therapeutic efficacy. Monte Carlo simulation was applied to develop individualized dosing regimens.

A one-compartment population pharmacokinetic model of teicoplanin was established using 328 blood concentration values from 195 patients. The population typical values of clearance and apparent volume of distribution of the model were 0.612 L·h^-1 and 91.2 L, respectively. Estimated glomerular filtration rate (eGFR) was included as a covariate for clearance, and albumin and urea were included as covariates for the apparent volume of distribution. The target values of PK/PD parameters were determined as trough concentration ≥15 mg·L^-1 and the ratio of 24 hour area under the drug-time curve to minimum inhibitory concentration (AUC₂₄/MIC)≥790. Several individualized dosing regimens were developed based on different levels of the model covariates.

For patients with hypoalbuminemia receiving teicoplanin, it is necessary to increase the dosage and frequency of the loading dose regimen according to the patients' albumin and eGFR levels, and adjust the maintenance dose regimen according to the MIC of pathogenic bacteria, so as to improve clinical efficacy.

To improve the allergic reaction test method of Cattle Encephalon Glycoside and Ignotin Injection by using the direct popliteal lymph node (D-PLNA) and reporter antigen popliteal lymph node (RA-PLNA) models in mice.

In the D-PLNA model, the Cattle Encephalon Glycoside and Ignotin Injection group, normal saline control group and positive drug D-penicillamine hydrochloride control group were set up. In the RA-PLNA model, the above groups were respectively added with reporter antigens TNP-Ficoll and TNP-OVA, and 50 μL of the drug was administered to the left toe pad. On the 7th day, the mice were sacrificed, and the popliteal lymph nodes were isolated, ground to prepare lymphocyte single-cell suspensions and counted to calculate the cell index. The cell suspension was cultured in 96-well plates, and after co-incubation with stimulators, the contents of IgE and MCP-1 in the cell supernatant were determined by ELISA.

Compared with the normal saline control group, in the RA-PLNA model of mice, the number of cells in the popliteal lymph nodes on the drug administration side increased in the group added with TNP-OVA (P < 0.05), and the contents of IgE and MCP-1 both increased (P < 0.05).

Cattle encephalon glycoside and ignotin injection only caused a positive lymph node reaction in mice when TNP-OVA was added, indicating that there may be small molecule substances in Cattle Encephalon Glycoside and Ignotin Injection that cooperate with TNP-OVA to induce allergic reactions.

To establish a UPLC-MS/MS method for the determination of genotoxic impurities dimethyl sulfate (DMS）and diethyl sulfate (DES) in Finerenone bulk drug.

The analytes were separated on an Agilent Poroshell 120 HILIC-Z (100 mm × 2.1 mm, 2.7 μm) column. The mobile phase consisted of a formic acid, water, and acetonitrile solution in a volume ratio of 0.5:300:700 (v/v/v). The flow was set at 0.3 mL·min^-1, with a column temperature of 30 ℃ . The target compounds were analyzed in the negative ion MRM mode.

DMS and DES showed good linear relationships within the ranges of 0.75-15.00 ng·mL^-1, with correlation coefficients (r) being 0.999 9. The detection limits of the method were 0.23 μg·g^-1 and the quantification limits were 0.75 μg·g^-1. The recoveries were both 107.53%-109.79%. No DMS and DES were detected in 3 batches of Finerenone.

This method is accurate, specific, and sensitive. It could be used for the simultaneous determination of DMS and DES in Finerenone bulk drug, thereby providing technical support for the quality control of Finerenone.

To establish a TLC identification method and the content determination of paeoniflorin in material benchmark of Huangqi Guizhi Wuwutang.

Thin-layer chromatography was employed for the identification of Astragali Radix (Astragalus root), Cinnamomi Ramulus (cinnamon twig), Paeoniae Radix Alba (white peony root) and Zingiberis Rhizoma Recens (fresh ginger) in material benchmark of Huangqi Guizhi Wuwutang. The quantitative analysis of paeoniflorin was performed by high performance liquid chromatography (HPLC) on a Thermo Hypersil GOLD C₁₈ column (4.6 mm × 250 mm, 5 μm). The mobile phase was acetonitrile-0.1% phosphoric acid solution (14:86) with isocratic elution; the flow rate was 1.0 mL·min^-1, the detection wavelength was 230 nm, and the column temperature was 25 ℃.

The linear range of paeoniflorin was 148.00-2 368.00 μg·mL^-1 (r = 0.999 9). The average recovery of paeoniflorin was 98.48% (RSD = 0.95%).

The established method is sensitive, simple, reliable and suitable for the quality control in the research and development of the classic formula Huangqi Guizhi Wuwutang.

To assess uncertainty in the determination of vortioxetine concentrations in serum from patients with psychiatric disorders using HPLC-MS/MS methodology.

For the determination of vortioxetine concentration in human serum, the uncertainty introduced by repeated measurements was evaluated using the type A evaluation. The uncertainties contributed from standard weighing, purity, solution preparation, preparation of drug-containing serum, extraction recovery, matrix effect, calibration curve fitting and instrumental precision were assessed using the type B evaluation. Subsequently, the synthetic and extended uncertainties were calculated.

The extended uncertainties for low (0.6 ng·mL^-1), medium (60 ng·mL^-1), and high (120 ng·mL^-1) concentrations of vortioxetine in human serum were 0.67, 4.10, and 10.49 ng·mL^-1, respectively, when confidence probability was P = 95% (k = 2).

The method employed in this study exhibits high accuracy and is suitable for the therapeutic drug monitoring of vortioxetine. The primary source of uncertainty arises from the calibration curve fitting, with particularly elevated uncertainty values introduced at the low concentration (0.6 ng·mL ^-1). Implementing a rational linear range and optimizing calibration curve fitting can enhance the accuracy of measurement results.