Objective To evaluate the quality of propranolol hydrochloride tablets based on national drug sampling,to analyze existing quality issues and improve their quality standards,to provide references and suggestions for the production,quality control,and supervision of this product.Methods A comprehensive evaluation of 178 batches of sampled products was conducted using legal standards combined with exploratory research,including key quality indicators such as related substances,dissolution,content uniformity,content determination,in vitro dissolution profiles,and genotoxic impurity N-nitrosoproranolol.The quality of domestic propranolol hydrochloride tablets and the controllability of the current quality standards for product quality were assessed.Results According to the legal standard methods,the qualification rate of 178 batches of sampled products was 100%.Exploratory research revealed that the impurity levels of samples from six manufacturing enterprises were far below the limit requirements;however,differences existed in genotoxic impurity N-nitrosoproranolol and other aspects.Conclusions The overall quality of propranolol hydrochloride tablets is good,but the current standards need further improvement.It is recommended to add/revise the detection methods for related substances,content,and content uniformity,strictly control N-nitrosoproranolol,and urge enterprises to pay attention to the quality of excipients and the control of the preparation production process.

Objective To establish a high-performance liquid chromatography method to detect the purity of human epidermal growth factor(hEGF),to compare the stability of the products of different enterprises by purity results,and to provide technical support for improving quality control and unified monitoring of hEGF based on national drug sampling and testing.Methods Agilent 300SB C8 column(250 mm×4.6 mm,5 μm)was used.Mobile phase A was 7.5 mmol·L-1 sodium phosphate buffer(pH 6.8),and mobile phase B was acetonitrile,the column temperature was 30℃,the flow rate was 0.6 mL·min-1 with gradient elution,and the detector wavelength was set at 280 nm.Results The resolution between the main peak of hEGF and the adjacent impurity peak was more than 1.5,with a detection limit of 6 ng.This method has been successfully applied to determine the purity of the bulk and final products.The results showed that the purity of the final products decreased compared with the bulk.The maximum impurity that increased significantly was the deamidation impurity identified by the mass spectrometry.Conclusion Based on the typical sample of the full chain and multi-dosage form,the established method had good specificity and resolution for the preliminary identification and purity determination of hEGF bulk and final products.

Objective To establish a high-throughput HPLC method for the simultaneous determination of 11 common antibacterial agents in acyclovir eye drops and to evaluate the quality and safety of the antibacterial agents in 42 batches of national drug inspection samples.Methods Gradient elution was performed on a Kromasil 100-5-C18(4.6 mm×250 mm,5 μm)column with acetonitrile-5 mmol·L-1 ammonium acetate aqueous solution(containing 1%triethylamine,pH adjusted to 4.5 by acetic acid)as the mobile phase.The detection wavelength was 262 nm.Results Good linear relationships were obtained for 11 antibacterial agents(r≥0.999 9).The average recovery range was 98.2%-101.8%,and the RSD was 0.7%-2.7%(n=9).As revealed by the systematic analysis of 42 batches of national drug inspection samples,some batches of samples were detected with out-of-prescription antibacterial agents 4-hydroxybenzoic acid and ethylparaben,and the results were 0.02-49 μg·mL-1.This indicated that ethylparaben degradation and colinear production pollution were the two major risk sources.Conclusions The method is accurate,sensitive,and specific and can be used for the qualitative and quantitative detection of antibacterial agents in acyclovir eye drops.Besides,some products have degradation of antibacterial agents and incomplete cleaning during co-linear production.It is still essential to further reinforce product quality control.

Objective To evaluate the quality profile of losartan potassium tablets in China based on national drug sampling and testing,to assess their safety,efficacy,and potential quality risks,and to provide evidence for improving quality standards along with feasible regulatory recommendations.Method A comprehensive evaluation was conducted on 196 sampled batches using statutory standards combined with exploratory studies,including tests for related substances,moisture,nitrites,nitrosamine,and azide genotoxic impurities.Results The compliance rate under statutory standards was 100%.However,exploratory analyses identified variations in moisture and nitrite levels among products,although genotoxic impurities and related substances were either undetectable or well below regulatory limits.Conclusions Losartan potassium tablets demonstrate satisfactory quality,though existing standards require further refinement by adding moisture and nitrite specifications.

Objective To establish a method for the simultaneous determination of peimine,peiminine,and hupehenine in Juhong pills,to investigate the raw material usage of Fritillaria thunbergii Miq.,and to preliminarily develop a detection approach for identifying adulteration with Fritillaria hupehensis Hsiao et K.C.Hsia.Methods The high-performance liquid chromatography-triple quadruple mass spectrometry(HPLC-MS/MS)was performed on an Agilent Poroshell 120 SB C18 column(2.1 mm×100 mm,2.7 μm)with a mobile phase consisting of acetonitrile-methanol(1∶1)and 0.1%formic acid under gradient elution.The flow rate was set at 0.3 mL·min-1.The column temperature was maintained at 35℃,and the injection volume was 2 μL.Electrospray ionization(ESI)in positive ion mode and multiple reaction monitoring were employed to quantify the three components in 170 batches of Juhong pills.Simulated positive samples with varying adulteration ratios of Fritillaria hupehensis Hsiao et K.C.Hsia were prepared to establish a simple yet efficient detection limit for adulteration.Results Three components showed good linear correlation within their ranges(r≥0.997 5),and the averaged recoveries ranged from 92.0%-106.2%.A total of 61 batches were suspected of Fritillaria thunbergii Miq.adulteration with Fritillaria hupehensis Hsiao et K.C.Hsia in raw material inputs,with the peimine to peiminine ratio below 1.15.Among these samples,27 batches were large honey-bound pills with hupehenine levels of 2.636-9.939 μg·g-1;34 batches were water-honeyed pills showing significantly higher hupehenine contamination at 6.752-48.137 μg·g-1.Conclusion The established method is simple,reliable,and accurate for the quality control of Fritillaria thunbergii Miq.adulteration in Juhong pills without imposing significant additional costs.

Objective To establish a gas chromatography-mass spectrometry method for simultaneous determination of the contents of volatile components muscone,menthol,borneol,isoborneol,camphor,and carvone in Wuli Huichun pills,and to evaluate the quality of Wuli Huichun pills based on authenticity,effectiveness and safety.Methods The ethyl acetate extract was analyzed by HP-5MS capillary column(30 m×0.25 mm,0.25 μm)with temperature programming.The injection port temperature was set at 230℃,and the split ratio was set at 10∶1.The carrier gas was high-purity helium gas.The injection port was in constant flow mode,with a carrier gas flow rate of 1.0 mL·min-1.The detector was a mass spectrometer with a triple quadrupole in series.The ion source was an electron bombardment source(EI)with a temperature of 250℃.The collision gas was argon.The temperature of the mass spectrometry transmission interface was 250℃.Scanning mode was SIM mode,with a solvent delay of 2 minutes.Results The linear relationships of the six components were good(r>0.999 0),the average recoveries were 93.57%-97.96%,and the RSD was 0.73%-2.5%.Conclusion The method is simple,accurate,and efficient,and can be used for the quality evaluation of Wuli Huichun pills.

Objective To systematically evaluate the quality of Fengshiding capsules,to analyze existing problems based on national drug sampling and testing,and to offer references and suggestions for improving quality control and regulatory supervision of this product.Methods A total of 136 batches of Fengshiding capsules were subjected to standard quality tests and exploratory analyses.HPLC was used to establish the content determination of Angelica dahurica,Cynanchum paniculatum,and Glycyrrhizae Radix,as well as the limit test for anabasine in the preparation.Additionally,an UPLC method was also employed to establish the characteristic chromatogram of Fengshiding capsules.A screening method for artificial pigments was developed,and UPLC-MS/MS was used to detect the illegal addition of chemical drugs in Fengshiding capsules.Results All 136 batches of samples passed inspection according to the current quality standards.However,based on exploratory study evaluations,the content determination results of Cynanchum paniculatum,Angelica dahurica,and Glycyrrhiza Radix were below the proposed limits.The limit test for anabasine did not exceed the proposed threshold.Furthermore,the characteristic chromatograms revealed missing peaks in several samples,and some batches contained artificial pigments and residues of acetaminophen.Conclusions The overall quality of Fengshiding capsules is rated as"average"based on national drug sampling and testing.To enhance product quality,it is recommended to improve quality standards,ensure the use of high-quality raw herbal materials,promote stronger internal oversight by manufacturers,and intensify regulatory supervision.

Objective To mine and analyze signals of acute kidney injury(AKI)related to drugs,comprehensively summarize the potential risk drugs,and provide a reference for clinically safe medication.Methods The AKI reports from January 2004 to September 2023 in the US FDA Adverse Event Reporting System(FAERS)were retrieved.Disproportionality methods were used to explore the relationship between drugs and AKI,and demographic information,time to onset,and patient outcomes were analyzed.Results Out of 1 253 drugs,159 were identified as AKI signal drugs.Among these,there were 49 antimicrobial agents(30.82%),including 35 antibiotics and 14 antiviral agents;33 antineoplastic agents(20.75%);and 25 hypotensive agents(15.72%).Drug-related AKI occurred mostly in the elderly,and the male-to-female ratio was 124∶100.The median time to onset for AKI related to antibiotics was≤8 d,with the third quartile≤21 d.Rivaroxaban and aspirin had higher proportions of death reports,with 33.03%and 31.44%respectively.Conclusions A multitude of drugs pose a risk for acute kidney injury,necessitating caution in their clinical application and the implementation of monitoring of renal function.The elderly are a high-risk group for drug-related AKI,and there are more males than females.For antibiotics,the first 21 days are the key monitoring period.For drugs that require long-term use,regular monitoring is necessary.

Objective To explore and evaluate the adverse drug events(ADE)signals of thromboembolic events induced by cisplatin and carboplatin,and to provide references for clinical safety and rational use of drugs.Methods The cisplatin-and carboplatin-related thromboembolic adverse events reports were collected from the U.S.FDA Adverse Event Reporting System(FAERS)database with the reporting time range from the first quarter of 2004 to the fourth quarter of 2023.Thromboembolic ADR signals were detected using the reporting odds ratio(ROR)method,the medicines and healthcare products regulatory agency(MHRA)method,and the Bayesian confidence propagation neural network(BCPNN)method at the SMQ level and preferred term(PT)level.Results A total of 1 959 cisplatin-related thromboembolism events and 2 524 carboplatin-related thromboembolism events were reported.In terms of gender composition,after excluding reports with unspecified gender,the ratio of male to female was 1.69∶1 for cisplatin and 0.65∶1 for carboplatin.For cisplatin,triple signals were generated at the"thromboembolic events"SMQ level as well as its sub-levels"venous thromboembolic events",and dual signals were generated at the"arterial thromboembolic events"sub-level.However,for carboplatin,dual signals were generated at the"thromboembolic events"SMQ level,and three signals were generated only at the"venous thromboembolic events"sub-level.The PT hierarchy analysis of thromboembolic events revealed that except for"thrombotic microangiopathy"produced single signal,signals generated by cisplatin were all triple signals,among which"aortic thrombosis"(ROR 95%CI lower limit=72.59,IC-2SD=5.93)exhibited the strongest signal intensity.Different from cisplatin,except for"acute myocardial infarction","ischemic stroke",and"cerebral infarction",which generated dual signals,"aortic thrombosis",which generated a single signal,all the other signals produced by carboplatin were triple signals.Additionally,"venous occlusive liver disease"(ROR 95%CI lower limit=11.58,IC-2SD=3.35)displayed the strongest signal intensity.Among various types of thromboembolic events,both cisplatin-and carboplatin-related"pulmonary embolism"and"deep vein thrombosis"were reported the highest number,ranking first and second,respectively.Conclusions In this study,cisplatin and carboplatin were proven to increase the risk of thromboembolic adverse events.Cisplatin was associated with potential risks of"venous thromboembolism"and"arterial thromboembolism",while carboplatin was associated with"venous thromboembolism".Therefore,attention should be paid to the above risks during clinical use.

Objective To explore and analyze the adverse drug event(ADE)signals associated with pembrolizumab and to provide a reference for the real-world safety of drug use on elderly patients.Methods ADE reports of pembrolizumab in the general population and elderly population were collected from the FDA Adverse Event Reporting System(FAERS)for the period between January 1st,2019,and June 30th,2024.Multiple signal detection methods(ROR,PRR,MHRA)were employed for data mining.Classification and statistical analysis were performed using the System Organ Class(SOC)and Preferred Term(PT)from the MedDRA(Version 27.1)dictionary.Results A total of 966 signals were identified in the general population,spanning 24 SOCs,while 593 signals were detected in the elderly population,spanning 23 SOCs.Comparative visualization analysis of critical PTs under four major SOCs revealed no significant abnormal signals in elderly patients.Conclusion A comprehensive and multidimensional analysis of the ADE data from the FAERS database indicates that pembrolizumab appears to be relatively safe for use in elderly patients.