Drug adulteration analysis based on complexation with cyclodextrin and metal ions using ion mobility spectrometry

Drug adulteration and contamination are serious threats to human health therefore,their accurate monitoring is very important.Allopurinol(Alp)and theophylline(Thp)are commonly used drugs for the treatment of gout and bronchitis,while their isomers hypoxanthine(Hyt)and theobromine(Thm)have no effect and affect the efficacy of the drug.In this work,the drug isomers of Alp/Hyt and Thp/Thm are simply mixed withα-,β-,γ-cyclodextrin(CD)and metal ions and separated using trapped ion mobility spectrometry-mass spectrometry(TIMS-MS).TIMS-MS results showed that Alp/Hyt and Thp/Thm isomers could interact with CD and metal ions and form corresponding binary or ternary complexes to achieve their TIMS separation.Different metal ions and CDs showed different separation effect for the isomers,among which Alp and Hyt could be successfully distinguished from the complexes of[Alp/Hyt+γ-CD+Cu–H]^(+)with separation resolution(RP–P)of 1.51;whereas Thp and Thm could be baseline separated by[Thp/Thm+γ-CD+Ca–H]^(+)with RP–P of 1.96.Besides,chemical calculations revealed that the complexes were in the inclusion forms,and microscopic interactions were somewhat different,making their mobility separation.Moreover,relative and absolute quantification was investigated with an internal standard to determine the precise isomers content,and good linearity(R^(2)>0.99)was obtained.Finally,the method was applied for the adulteration detection where different drugs and urine were analyzed.In addition,due to the advantages of fast speed,simple operation,high sensitivity,and no chromatographic separation required,the proposed method provides an effective strategy for the drug adulteration detection of isomers.

Theoretical and experimental research on static stiffness,performance,and lift-off characteristics of multi-layer gas foil thrust bearings

In this study,a new comprehensive fully coupled elastic–hydrodynamic model is developed for a multi-layer gas foil thrust bearing(GFTB).The interaction effects among the top foil,back board,middle foil,and bottom foil,as well as the Coulomb friction effect,are considered.The stiffness and static characteristics obtained by the experimental and theoretical approaches are in good agreement,which verifies the accuracy of the model.The contribution of each foil layer to the overall stiffness and the load-carrying mechanism are analyzed.Interaction effects of the load,preload,and rotational speed on the static performance are investigated comprehensively.Furthermore,start–stop tests are performed to achieve the lift-off speed,start-up torque,and shut-down torque under various operating conditions.

Applications and recent advances in transdermal drug delivery systems for the treatment of rheumatoid arthritis

Rheumatoid arthritis is a chronic,systemic autoimmune disease predominantly based on joint lesions with an extremely high disability and deformity rate.Several drugs have been used for the treatment of rheumatoid arthritis,but their use is limited by suboptimal bioavailability,serious adverse effects,and nonnegligible first-pass effects.In contrast,transdermal drug delivery systems(TDDSs)can avoid these drawbacks and improve patient compliance,making them a promising option for the treatment of rheumatoid arthritis(RA).Of course,TDDSs also face unique challenges,as the physiological barrier of the skin makes drug delivery somewhat limited.To overcome this barrier and maximize drug delivery efficiency,TDDSs have evolved in terms of the principle of transdermal facilitation and transdermal facilitation technology,and different generations of TDDSs have been derived,which have significantly improved transdermal efficiency and even achieved individualized controlled drug delivery.In this review,we summarize the different generations of transdermal drug delivery systems,the corresponding transdermal strategies,and their applications in the treatment of RA.

ETME,a novel β-elemene derivative,synergizes with arsenic trioxide in inducing apoptosis and cell cycle arrest in hepatocarcinoma cells via a p53-dependent pathway

Arsenic trioxide(ATO)has been identified as an effective treatment for acute promyelocytic leukemia(APL)but is much less effective against solid tumors such as hepatocellular carcinoma(HCC).In the search for ways to enhance its therapeutic efficacy against solid tumors,we have examined its use in combination with a novel derivative ofβ-elemene,N-(β-elemene-13-yl)tryptophan methyl ester(ETME).Here we report the effects of the combination on cell viability,apoptosis,the cell cycle and mitochondria membrane potential(MMP)in HCC SMMC-7721 cells.We found that the two compounds acted synergistically to enhance antiproliferative activity and apoptosis.The combination also decreased the MMP,down-regulated Bcl-2 and pro-proteins of the caspase family,and up-regulated Bax and BID,all of which were reversed by the p53 inhibitor,pifithrin-α.In addition,the combination induced cell cycle arrest at the G2/M phase and reduced tumor volume and weight in an xenograft model of nude mice.Overall,the results suggest that ETME in combination with ATO may be useful in the treatment of HCC patients particularly those unresponsive to ATO alone.