Development and validation of an LC-MS/MS assay for the quantification of efavirenz in different biological matrices.
OBJECTIVE
The non-nucleoside reverse transcriptase inhibitor efavirenz is one of the most prescribed antiretroviral therapeutics. Efavirenz-containing therapy has become associated with the occurrence of CNS side effects, including sleep disturbances, depression and even psychosis.


RESULTS
The investigation of efavirenz distribution required the development of a versatile and sensitive method. In addition to plasma, quantification was required in brain tissue and phosphate-buffered saline. The assay presented here was linear from 1.9 to 500 ng/ml. Accuracy and precision ranged between 93.7 and 99.5%, and 1.5 and 5.6%, respectively.


CONCLUSIONS
The method developed here represents a versatile, sensitive and easy-to-use assay. The assay has been applied to in vitro and in vivo samples demonstrating reliable efavirenz quantification in multiple matrices.
Molecular & Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
Paul
P
Curley
Molecular & Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
Marco
M
Siccardi
Molecular & Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
Darren M
DM
Moss
Molecular & Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.|European Nanomedicine Characterisation Laboratory, Molecular & Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
Andrew
A
Owen
D000480:Alkynes; D000818:Animals; D048588:Benzoxazines / Q000032:analysis* / Q000097:blood / Q000592:standards; D001921:Brain / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid / Q000592:standards; D019963:Clinical Chemistry Tests / Q000379:methods*; D003521:Cyclopropanes; D008297:Male; D011786:Quality Control; D051381:Rats; D017208:Rats, Wistar; D018894:Reverse Transcriptase Inhibitors / Q000032:analysis* / Q000097:blood / Q000592:standards; D053719:Tandem Mass Spectrometry / Q000592:standards
D000480:Alkynes; D048588:Benzoxazines; D003521:Cyclopropanes; D018894:Reverse Transcriptase Inhibitors; C098320:efavirenz
LC–MS/MS; brain tissue; efavirenz; plasma; protein binding