Correlation Of Plasma Ketamine Concentrations With Saliva And Urine Concentrations On Rabbits

Objective To develop a qualitative and quantitative method for the simultaneous determination of ketamine and its main active metabolite norketamine in saliva by GC and GC/MS.Studies of the correlation of plasma concentrations of ketamine and its metabolite with saliva and urine concentrations in acute toxic rabbits after intragastric administration(i.g.)and intravenous injection(i.v.)of ketamine.Methods 1.Analytical method of saliva samples:The acute toxic rabbits were divided into two groups of pilocarpine stimulating group and non stimulating group.Collected their saliva at different time points after drug administration.Compared the concentrations of ketamine and norketamine between two groups by t-test.Saliva samples were alkalized and extracted with ethyl acetate after adding SKF_525A(Internal Standard,IS).The extracts were qualitated by GC/MS full sacn method and quantitated by GC analysis.2.Correlation study:The rabbits were given hydrochloride of ketamine with a dose of LD₅₀ by i.g.administration and i.v.injection.To collect their saliava,plasma and urine at different time points after drug administration.The concentrations of ketamine and norketamine were determined by GC.Analysis of the correlation of plasma concentrations of ketamine and its metabolite with saliva and urine concentrations by bivariate correlation analysis methods.Results 1.The qualitated and quantitated methods of ketamine and norketamine in saliva were established.The linear range for ketamine and norketamine in saliva was 0.01～10μg·mL^-1. The limit of detection was 0.005μg·mL^-1.The analytical recovery was 95.03%～105.35%.The inter- and intra-day relative standard deviations of precisions were less than 10.0%.There was significant difference between pilocarpine stimulating group and non stimulating group(P＞0.05).2.In i.g.administration group,the concentrations of ketamine and norketamine in plasma had high correlation with that in saliva.The correlation coefficient(r)was 0.88～0.95,0.86～0.96,respectively.The average of that was 0.912 and 0.914.In i.v.injection group,the concentrations of ketamine and norketamine in plasma had correlation with that in saliva too. The correlation coefficient(r)was 0.8～0.96,0.86～0.95,respectively.The average of that was 0.899 and 0.912.In i.g.administration group,the concentrations of ketamine and norketamine in plasma had midrange correlation with that in urine before 240min.The average of correlation coefficient was 0.596 and 0.606 before 240min and lower than 0.5 after 240min.In i.v.injection group,the concentrations of ketamine and norketamine in plasma had midrange correlation with that in urine before 180min.The average of correlation coefficient was 0.615 and 0.620 before 180min and lower than 0.5 after 180min.Conclusion 1.The GC/MS and GC methods established for the simultaneous determination of ketamine and its metabolite norketamine in saliva proved to be simple,sensitive and reproducible and could be applied to analyse in toxication and abuse cases of ketamine rapidly.2.The concentrations of ketamine and norketamine in plasma had high correlation with that in saliva in two groups.In i.g.administration group and i.v.injection group,the concentrations of ketamine and norketamine in plasma had midrange correlation with that in urine before 240min and 180min respectively,and the correlation coefficient was lower than 0.5 after 240min and 180min respectively.Saliva analysis could be used in case of ketamine abused and concluding the ketamine concentration in plasma in clinical drug monitoring and forensic medicine.The correlation between plasma concentrations of ketamine and norketamine and urine concentrations were lower than plasma concentrations and saliva concentrations.Urine concentrations of ketamine and norketamine couldn't reflect directly plasma concentrations,so it should be considered carefully when concluding plasma concentrations of ketamine and norketamine by urine concentrations.