Correlation Of Pethidine Concentration In Plasma With Concentration In Saliva And Urine

ObjectiveTo develop an animal model for intravenous administration of pethidine to rabbits and a method for extracting and analyzing of pethidine in biological samples by GC/MS and GC/NPD. To study the correlation of plasma concentrations of pethidine with saliva and urine concentrations in acute poisoning rabbits after intravenous injection of pethidine. The research results might provide a reference basis for sampling and evaluating analysis results in pethidine abused cases.Methods1. The extraction method of pethidine in body fluids:Chose the best extracted condition of pethidine in body fluids by compared the extraction results of pethidine which were extracting by different extractants at pH9and pH12respectively.2. The analysis method of pethidine:The biological samples were alkalified and extracted by dichloromethane after adding lidocaine(internal standard, IS). The extracts were qualitative analyzed by GC/MS and quantitative analyzed by GC/NPD with internal standard and working curve methods.3. Correlation study in body fluids:The rabbits in experimental group were intravenous injection of pethidine with a dose of20mg·kg-1and in control group were intravenous injection of corresponding amount of physiologic saline. The rabbits’ saliva, plasma and urine were collected at different time points(15,30,45,60,120,180,240,360,480,600min). The concentrations of pethidine were determined by GC/NPD. The correlation of plasma concentrations of pethidine with saliva and urine concentrations were analyzed by bivariate correlation analysis methods. Results1. The extraction condition of pethidine in body fluids was selected at pH12, and extracted by dichloromethane.2. The qualitative and quantitative methods of pethidine in biological samples were established. The linear range for pethidine in plasma was2.0～100.0μg·mL-1and in urine was2.0～200.0μg·mL-1.The limit of detection in plasma and urine were both2.00μg·mL-1(S/N≥3). The analytical recovery was98.80%～114.72%. The inter-and intra-day relative standard deviations of precisions were less than2.0%.3. After intravenous injection of pethidine to rabbits, the pethidine concentration ratio in saliva and plasma(S/P) was0.9844-1.3372in60mins, while S/P was1.8596～2.8310from120min to600min. The pethidine concentration ratio had large fluctuation in60mins not only in plasma and urine(P/U) but also in saliva and urine(S/U), and tending towards stability from120min to600min, P/U and S/U were0.0192～0.1482and0.0396-0.2308respectively.4. After intravenous injection of pethidine to rabbits, the concentrations of pethidine in plasma had high correlation with that in saliva, the correlation coefficient (r) was0.971(P<0.05). The correlation coefficient (r) was-0.800(P<0.01) between plasma and urine concentrations of pethidine, and-0.721between urine and saliva concentrations of pethidine (P<0.05).ConclusionAfter intravenous injection of pethidine to rabbits, there is a good linear correlation about pethidine content between in plasma and saliva. The study results suggest that saliva can be considered as a substitute of plasma in pethidine abused cases and clinical drug monitoring. The pethidine content in plasma can be concluded from pethidine content in saliva. As the poor linear correlation and variation of pethidine content between in urine and plasma or between in urine and saliva, pethidine content in plasma or in saliva could not be concluded directly by that in urine.