OBJECTIVES: Patients with heart failure with reduced ejection fraction (HFrEF) often require diuretics during hospitalization to alleviate fluid retention and improve prognosis. However, the diuretic efficacy and renal impact of dapagliflozin in this population remain unclear. This study aims to investigate the effects of dapagliflozin on diuresis and renal function in hospitalized patients with HFrEF. METHODS: This retrospective analysis included clinical data from 200 hospitalized HFrEF patients treated at Xiangya Hospital of Central South University between January 2021 and September 2022. Patients were divided into 2 groups based on whether they received dapagliflozin: a standard treatment group (n=120) and a dapagliflozin treatment group (n=80). The following were compared between the 2 groups during hospitalization: The 24-hour average difference of liquid intake and output during the first 5 days, urine output, cumulative urine output, diuretic efficiency, estimated glomerular filtration rate (eGFR), N-terminal pro B-type natriuretic peptide (NT-proBNP), hospitalization costs, drug costs, and cost-effectiveness ratio (C/E). RESULTS: 1) Primary outcome: The 24-hour average difference of liquid intake and output during the first 5 days was significantly higher in the dapagliflozin treatment group than in the standard treatment group (P<0.05). 2) Secondary outcomes: The 24-hour average urine volume, cumulative urine volume and diuretic efficiency in the first 5 days of dapagliflozin treatment group were higher than those in the standard treatment group, and the differences were statistically significant (all P<0.05). Among patients with impaired renal function on admission [eGFR between 45 and 90 mL/(min·1.73 m²)], the change in eGFR after treatment was significantly smaller in the dapagliflozin treatment group (P<0.05). For patients with normal renal function on admission [eGFR >90 mL/(min·1.73 m²)], the difference in eGFR changes between 2 groups was not significant (P>0.05). NT-proBNP decreased more in the dapagliflozin treatment group than in the standard treatment group during hospitalization (P<0.05). 3) Other indicators: The length of hospital stay was longer in the dapagliflozin treatment group. However, discharge systolic blood pressure, drug costs, and hospitalization costs were all higher in the standard group, though differences were not statistically significant (all P>0.05). The C/E was more favorable in the dapagliflozin treatment group (425.36 vs. 476.67). CONCLUSIONS In hospitalized patients with chronic HFrEF, dapagliflozin treatment increased 24-hour average difference of liquid intake and output and total urine output, reduced NT-proBNP levels, and showed a milder decline in eGFR in those with pre-existing renal impairment. Discharge blood pressure, drug costs, and hospital stay were not significantly affected. While standard therapy may offer better short-term clinical benefits, dapagliflozin demonstrated a superior short-term cost-effectiveness profile.
Humans ; Benzhydryl Compounds/pharmacology* ; Glucosides/pharmacology* ; Retrospective Studies ; Male ; Female ; Heart Failure/physiopathology* ; Hospitalization ; Middle Aged ; Aged ; Glomerular Filtration Rate/drug effects* ; Diuretics/therapeutic use* ; Kidney/drug effects* ; Natriuretic Peptide, Brain/blood* ; Stroke Volume ; Peptide Fragments/blood* ; Diuresis/drug effects*

Objective To develop a detection method with ultra-high performance liquid chromatogra-phy-high resolution mass spectrometry(UPLC-HRMS) for fast screening of doping substances in pastes,so as to strengthen the drug-borne doping risk prevention system.Methods The paste samples were removed the covering film and extracted by using tert-butyl methyl ether and anhydrous ethanol,respectively.The extracts were combined and blown dry under nitrogen flow at 40 ℃,and methanol was used to dissolve the residues,which were then filtered and analyzed with the Thermo Vaniquish-Q Exactive Plus.Then,3 μL of the solution was injected into and separated by the Agilent ZORBAX-Eclipse C18 column (2.1 × 100 mm,1.8 μm),and the gradient elution was performed with 10 mM ammonium formate (containing 0.1％ formic acid,pH3.5) and acetonitrile as mobile phase.The 170 kinds of doping substances were detected in positive ion electrospray (ESI+) and negative ion electro-spray(ESI-) respectively under Full Mass/data-dependent mass spectrometry(Full MS/ddMS2) mode.Re-sults The results showed that the method had good selectivity and samples were stable within 48 h af-ter pretreatment.The detection limit(LOD) of 92 doping substances were about 3 ng/g,while that of another 31 and 47 ones was about 6 ng/g and 30 ng/g,respectively.In this study,among 10 paste samples,4 were tested positive for strychnine,and 3 were positive for higenamine and ephedrine,re-spectively.Conclusion A fast screening method for 170 kinds of doping substances in 9 categories is developed by using ultra-high performance liquid chromatography with high resolution mass spectrome-try in this study.Such method proves to be simple,sensitive and reliable,which is suitable for fast screening of doping substances in pastes.

Objective To develop a detection method with ultra-high performance liquid chromatogra-phy-high resolution mass spectrometry(UPLC-HRMS) for fast screening of doping substances in pastes,so as to strengthen the drug-borne doping risk prevention system.Methods The paste samples were removed the covering film and extracted by using tert-butyl methyl ether and anhydrous ethanol,respectively.The extracts were combined and blown dry under nitrogen flow at 40 ℃,and methanol was used to dissolve the residues,which were then filtered and analyzed with the Thermo Vaniquish-Q Exactive Plus.Then,3 μL of the solution was injected into and separated by the Agilent ZORBAX-Eclipse C18 column (2.1 × 100 mm,1.8 μm),and the gradient elution was performed with 10 mM ammonium formate (containing 0.1％ formic acid,pH3.5) and acetonitrile as mobile phase.The 170 kinds of doping substances were detected in positive ion electrospray (ESI+) and negative ion electro-spray(ESI-) respectively under Full Mass/data-dependent mass spectrometry(Full MS/ddMS2) mode.Re-sults The results showed that the method had good selectivity and samples were stable within 48 h af-ter pretreatment.The detection limit(LOD) of 92 doping substances were about 3 ng/g,while that of another 31 and 47 ones was about 6 ng/g and 30 ng/g,respectively.In this study,among 10 paste samples,4 were tested positive for strychnine,and 3 were positive for higenamine and ephedrine,re-spectively.Conclusion A fast screening method for 170 kinds of doping substances in 9 categories is developed by using ultra-high performance liquid chromatography with high resolution mass spectrome-try in this study.Such method proves to be simple,sensitive and reliable,which is suitable for fast screening of doping substances in pastes.

Objective To introduce a practical high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS)method for the detection of seven growth hormone-releasing peptides (GHRPs)including GHRP-1,GHRP-2,GHRP-4,GHRP-5,GHRP-6,Hexarelin and Alexamorelin and two growth hormone secretagogues(GHS)including anamorelin and ipamorelin,and study the stability of these nine substances in the human urine.Method The urine samples were purified and extracted by a solid phase extraction procedure using Oasis(R) WCX column.The urine was first centrifuged and taken out 1 mL into a small column,cleaned by 5％ NH4OH and 20％ CH3CN respectively,eluated using the mixture of water and acetomitrile(1/3)with 2％ formic acid,blow-dried in the nitrogen at 35℃ and finally redissolved to be injected into the LC-MS/MS.Result The limits of detection were between 0.01～0.5 ng/mL accordingly.The spiked recoveries at the low concentration(1 ng/mL),medium concentration(2 ng/mL)and high concentration(10 ng/mL)ranged between 40％ and 76％.The intra-and interday precisions of the target substances at these three concentrations were all less than 15％.The indoor temperature,refrigeration condition and multigelation were observed to have significant impact on the anamorelin,GHRP-2,GHRP-4 and GHRP-5.Conclusion The method established in this study is simple,and its specificity and sensitivity meets the international standard and technical documents for laboratories set up by the Wworld Anti-Doping Agency.It has been applied in our routine work.Multigelation should be avoided in the transport,detection and long-term laboratory storage of urine samples.

A method was evaluated for determination of twenty-one doping (including nandrolone, boldenone and methandienone) in human urine by gas chromatography-high resolution mass spectrometry. Samples were prepared by liquid-liquid extraction, concentrated, TMS derivatization and limit of detection at ng x mL(-1) by MID/GC/HRMS. According to the code of the World Anti-Doping Agency (WADA), precision and recoveries of the procedure were evaluated by replicate analysis (n = 6), the recoveries in the range of 66%-103%, with the RSD below 10.0%. The precision within the day of the method with three different concentrations was also determined RSD were less than 9.5%, 10.0% and 9.7%.

Objecave To develop a sensitive and specific LC-MS/MS method for determination of testolactone in human urine.Methods A C_(18 )column(2.1×50mm,3.5μm) was used.The mobile phase Was a mixture of acetonitrile and the buffer solution(ammonium acetate-water solution adjusted with formic acid to pH 3.5)at a flow rate of 0.5ml/min.A mass spectrometer equipped with electrospray ionization source was used as a detector and operated in the positive mode.In multiple reaction monitoring(MRM)mode,the ion transitions of m/z 301→121 and m/z 301→25 was used to qualify and quantify the testolactone,respectively.Results Chromatograms showed no endogenous interfering peaks with the urine blank sample.Each analysis was completed within 7min The calibration wag linear in the concentration range within 0.1～50μg/ml.The intra-batch and inter-batch RSD were less than 10%.The recovery rate of the extraction was about 60%.Conclusions The method is proved to meet the requirements of WADA and be suitable for routine screening.

In this article,anti-doping techniques including sample preparation,isolation and analysis,were reviewed.On-line solid-phase extraction with column-switching technique and High through rapid analysis were also discussed.