Drug adulteration analysis based on complexation with cyclodextrin and metal ions using ion mobility spectrometry / 药物分析学报

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 with α-,β-,y-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 iso-mers 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+y-CD+Cu-H]+with separation resolution(Rp-p)of 1.51;whereas Thp and Thm could be baseline separated by[Thp/Thm+y-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(R2＞0.99)was ob-tained.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.

Investigation of Protonated and Lithiated Leucine-Enkephalin by Hydrogen/Deuterium Exchange and Theoretical Calculations / 分析化学

Differences of protonated and lithiated leucine-enkephalin(LE) were investigated by hydrogen deuterium exchange-mass spectrometry(HDX-MS) combined with quantum chemistry calculation. The results revealed that the protonated ions possessed very high product yield with all hydrogen atoms being exchanged, while the reaction of lithiated LE stopped after exchanging five hydrogen atoms in the same experimental conditions. The different HDX behaviours probably indicated their conformational differences. To further clarify the experimental results, the most stable conformations of protonated and lithiated leucine-enkephalin were calculated by density functional theory. It was found that terminal amino group was the most thermodynamically stable protonation site,while Li+in coordination of four carbonyl oxygen atoms formed the most favourable lithiated LE. The reaction field reduction of lithium LE was probably due to the less acidity of hydrogen atoms and the increasing rigid conformation change induced by lithium ion.

Investigation of Non-covalent Interactions of 18-Crown-6 with Amino Acids in Gas Phase by Mass Spectrometry / 分析化学

The non-covalent interactions between 18-crown-6 (18c6) and 20 common types of protonated amino acids were explored by electrospray ionization mass spectrometry (ESI-MS).The mass spectra showed the formation of 1:1 stoichiometric non-covalent complexes between 18c6 and amino acids.The calibration curves and linear equations for the complexes of L-Phe,L-Tyr,L-Lys and L-Asp with 18c6 were established by mass spectrometric titration and used as reference values for competitive ESI-MS.Through competitive equilibrium,the binding constants for the complexes of 18c6 with other L-amino acids and their D-isomers were derived.It was found,as a general trend,lgKa for the complexes of 18c6 with the basic amino acid and the amino acid with alkyl side chain were larger than other complexes,and among the amino acids with alkyl side chain,Gly and Ala exhibited greater 18c6 binding affinities.As for Ser and Thr,the intramolecular hydrogen bond between the nitrogen atom from terminal NH2and the oxygen atom from carboxyl may impede their protonated amino-group to attack the 18c6.Furthermore,Gln and Asn exhibited lower 18c6 binding affinities probably due to effects of electron-withdrawing group of acylamide.Finally,the chiral selectivity of 18c6 for 19 L-,or D-amino acids was measured by ESI-MS,indicating 18c6 could only recognize some neutral amino acid isomers.