A novel method for the separation and determination of non-encapsulated pyrene in plasma and its application in pharmacokinetic studies of pyrene-loaded MPEG-PLA based nanoparticles.
During the pharmacokinetic processes of nanoparticles, encapsulated drugs and non-encapsulated (free and protein-bound) drugs are the drug forms existing in plasma. It is necessary and important to measure the bioavailable drug concentration, namely, the non-encapsulated drug concentration, in pharmacokinetic studies of nanoparticles. A new method using liquid-liquid extraction was first developed and validated for the separate determination of non-encapsulated drugs in plasma. The method was based on the significant difference of extractability between non-encapsulated and encapsulated drugs, and used n-heptane as an extractant. Satisfactory results were obtained with a good linear relationship in the range of 1-80 ng ml(-1) (r = 0.9999) and good reproducibility with coefficients of variation (CVs) less than 10% of intra- and inter-day evaluation results, and the accuracy of intra- and inter-day evaluation results ranged from 92.4% to 109.2%. The extraction recovery was stable in the range 68.6%-75.6%. The developed method had been proven to be an ideal method with high specificity and sensitivity, and the method is simple and rapid. The method described herein has been successfully applied for pharmacokinetic studies in female Wistar rats after the administration of a 5 mg equivalent pyrene kg(-1) dose of pyrene-loaded nanoparticles. The results showed that the non-encapsulated drug had a different pharmacokinetic behavior compared with that of the total drug.
Zhao
Xiaozhi
X
College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
Mou
Dongsheng
D
Wan
Jiangling
J
Xu
Huibi
H
Yang
Xiangliang
X
D000818:Animals; D004355:Drug Stability; D005260:Female; D016018:Least-Squares Analysis; D016014:Linear Models; D053758:Nanoparticles / Q000032:analysis / Q000737:chemistry*; D010599:Pharmacokinetics; D010949:Plasma / Q000737:chemistry*; D011091:Polyesters / Q000032:analysis / Q000493:pharmacokinetics*; D011092:Polyethylene Glycols / Q000032:analysis / Q000493:pharmacokinetics*; D011721:Pyrenes / Q000032:analysis / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results; D012997:Solvents
D011091:Polyesters; D011721:Pyrenes; D012997:Solvents; C492425:methoxy poly(ethylene glycol)-poly(lactide); D011092:Polyethylene Glycols; C030984:pyrene