Blood sampling without blood draws for in vivo pharmacokinetic studies in rats.
OBJECTIVE
Pharmacokinetic (PK) studies in rats typically involve removal of serial blood samples following dosing. This research illustrates the development of a fast in vivo microextraction technique that has the potential to partly replace current sampling techniques based on blood draws, especially in the case of small animals.


METHODS
The proposed sampling procedure is based on solid phase microextraction (SPME), an approach that has continued to revolutionize sampling and sample preparation ever since its discovery a decade ago. In vivo microextraction is faster than conventional methods, interferes minimally with the investigated system, minimizes errors associated with sample preparation and limits exposure of lab personnel to hazardous biological samples.


RESULTS
Here we show the successful application of fast microextraction during a full PK study with diazepam in rats. The results were found to correlate very well with a standard analytical method. Three calibration strategies--external, standard on the fiber, and double extraction--were employed to correlate the amount extracted with the in vivo concentration.


CONCLUSIONS
Our results demonstrate the unique advantages of this technique and highlight its utility as a valuable new tool for fast bioanalysis in support of in vivo sampling and PK studies, particularly during the early drug discovery process. This approach can be used not only for drugs, but also for other exogenous or endogenous compounds.
Musteata
Florin Marcel
FM
School of Pharmacy, Memorial University of Newfoundland, St. John's, NL, Canada.
de Lannoy
Inés
I
Gien
Brad
B
Pawliszyn
Janusz
J
D000097:Acetonitriles / Q000737:chemistry; D000818:Animals; D014151:Anti-Anxiety Agents / Q000097:blood* / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002021:Buffers; D002138:Calibration; D003975:Diazepam / Q000097:blood* / Q000493:pharmacokinetics*; D006207:Half-Life; D006863:Hydrogen-Ion Concentration; D008140:Lorazepam / Q000737:chemistry; D008297:Male; D008657:Metabolic Clearance Rate; D010710:Phosphates / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D012015:Reference Standards; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012965:Sodium Chloride / Q000737:chemistry; D052617:Solid Phase Microextraction / Q000379:methods*; D012996:Solutions / Q000737:chemistry; D013678:Technology, Pharmaceutical
D000097:Acetonitriles; D014151:Anti-Anxiety Agents; D002021:Buffers; D010710:Phosphates; D012996:Solutions; D012965:Sodium Chloride; D008140:Lorazepam; D003975:Diazepam; C032159:acetonitrile