| Pharmaceutical and personal care products(PPCPs)in the process of production and usage were released to surface water environment.PPCPs as emerging contaminants are attracting increasing attention due to the ubiquitous detection and potential risk in the environment.Chiral pharmaceuticals were detected in range of ng/L-μg/L in the environment.Due to the different biological activities,metabolic pathways and toxicities of chiral pharmaceutical enantiomers,the studies on occurrence and stability of enantiomers in the environment are necessary.The enantioseparation and determination method of seven chiral pharmaceuticals using high performance liquid chromatogram(HPLC)and ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)with vancomycin chiral stationary phase(CSP)was developed and optimized respectively.The enantioseparation mechanisms were explored by molecular docking technology(Autodock 4.0)and thermodynamic analysis method.Based on the optimized method,the distribution and pollution level of typical chiral pharmaceuticals in Xi River located in Liao River Basin were determinaed.The main results were obtained as follows:(1)Through investigating the effect of mobile phase additives,flow rate and column temperature on the retention and enantioseparation properties of these pharmaceuticals with HPLC,it was indicated that the optimal chromatographic condition to separate six pharmaceuticals(propranolol,atenolol,metoprolol,venlafaxine,fluoxetine and amlodipine)on vancomycin CSP was achieved using methanol as a main mobile phase with triethylamine(TEA)and glacial acetic acid(HOAc)added as modifiers in volume ratio of 0.01%at a flow rate of 0.3 mL/min and at a column temperature of 5℃.The optimal chromatographic condition for enantioseparation of chlorphenamine maleate was TEAA:THF=95:5(v/v),pH value of 3,flow rate of 0.3 mL/min,temperature of 15℃.The molecular docking technology(Autodock 4.0)was applied to simulate the combination of enantiomers and CSP,with thermodynamic analysis as the corroboration evidence.The result showed that obtained steady combination energy(ΔG)was consistent with the peak sequence of enantiomers.Therefore,the molecular docking technology could be as a tool to explain the enantioseparation mechanisms and predict peak sequence of chromatography.(2)A method for quantitative enantioseparation and determination of five chiral pharmaceuticals(propranolol,atenolol,metoprolol,venlafaxine and fluoxetine)residues in aquatic samples was optimized using solid phase extraction(SPE),followed by UPLC-MS/MS determination with vancomycin CSP.Under multiresponse monitoring and positive ion mode and using methanol-10 mmol/L of ammonium acetate(v/v 95:5)as mobile phase,the limit of detection(LOD)of analytical method was below 1.5 μg/L with 5-500 μg/L linearity range and correlation coefficient more than 0.994.Using Oasis(?)HLB cartridges for extraction of target chiral pharmaceuticals in water samples,the recovery was in the range of 47-123%with relative standard deviation(RSD)no more than 0.53%.(3)Xi River,Hun River tributary in Liao River Basin was selected for the water sampling from upstream,drain outlet and downstream of municipal sewage plant Target pharmaceuticals(propranolol,atenolol,metoprolol,venlafaxine and fluoxetine)were determined and found in the concentration range of 3.17-244 ng/L with detection frequency of 100%.The contaminants with highest concentration were metoprolol and atenolol,propranolol,venlafaxine and fluoxetine.Comparing with other rivers,the contamination level of target pharmaceuticals in Xi River was slightly higher.The chiral pharmaceuticals presented non-racemic profiles with enantiomer fraction(EF)of 0.42-0.52.The ecological risk of pharmaceuticals enantiomers was insignificant for D magna,but that of five pharmaceuticals was in the medium level with the joint risk quotient value(RQsum)of 0.13-0.44.Particularly,due to their high toxicity,venlafaxine and fluoxetine should be strictly controlled by government department. |
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