A sensitive and rapid liquid chromatography-tandem mass spectrometry method for the quantification of the novel neurokinin-1 receptor antagonist aprepitant in rhesus macaque plasma, and cerebral spinal fluid, and human plasma with application in translational NeuroAIDs research.
A sensitive and rapid liquid chromatography-tandem mass spectrometry method has been developed for to assess therapeutic exposures of aprepitant in HIV-infected patients and rhesus macaques. The method utilized a simple sample-preparation procedure of protein precipitation with methanol. Chromatographic separation was performed on a reversed phase C(8) column (Hypersil Gold, 50 mm x 2.1 mm, 3 microm) using a mobile phase composed of acetonitrile and water in 0.5% formic acid through gradient elution. Electro-spray ionization in positive mode was incorporated in the tandem mass spectrometric detection. The lower limit of quantitation of aprepitant in plasma of rhesus macaques and human and cerebral spinal fluid of rhesus macaques were 1, 1, and 0.1 ng/mL, respectively. The method has been successfully employed to measure aprepitant in preclinical and clinical samples collected from three SIV-infected rhesus macaques and ten patients with HIV infection. In conclusion, this liquid chromatography-tandem mass spectrometry method is suitable for preclinical-clinical translational research exploring exposure-response relationships with aprepitant as well as therapeutic drug monitoring of aprepitant.
Wu
Di
D
Laboratory for Applied PK/PD, Division of Clinical Pharmacology and Therapeutics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA. wudi@email.chop.edu
Paul
Dustin J
DJ
Zhao
Xianguo
X
Douglas
Steven D
SD
Barrett
Jeffrey S
JS
D015526:AIDS Dementia Complex / Q000188:drug therapy*; D000818:Animals; D000077608:Aprepitant; D002138:Calibration; D002851:Chromatography, High Pressure Liquid; D003362:Cost-Benefit Analysis; D015658:HIV Infections / Q000097:blood / Q000134:cerebrospinal fluid; D006801:Humans; D008253:Macaca mulatta; D009025:Morpholines / Q000032:analysis* / Q000097:blood / Q000134:cerebrospinal fluid; D064729:Neurokinin-1 Receptor Antagonists; D011786:Quality Control; D012015:Reference Standards; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry
D009025:Morpholines; D064729:Neurokinin-1 Receptor Antagonists; D000077608:Aprepitant