Simultaneous determination of 2',3'-dideoxyinosine and the active metabolite, 2',3'-dideoxyadenosine-5'-triphosphate in human peripheral-blood mononuclear cell by HPLC-MS/MS and the application to cell pharmacokinetics.
A specific and reliable HPLC-MS/MS method was developed and validated for the simultaneous determination of 2',3'-dideoxyinosine (ddI) and the active metabolites, 2',3'-dideoxyadenosine-5'-triphosphate (ddA-TP) in human peripheral-blood mononuclear cell for the first time. The analytes were separated on a HILIC column (100mm×2.1mm, 1.7μm) and a triple-quadrupole mass spectrometry equipped with an electrospray ionization (ESI) source was used for detection. The cell homogenates sample was prepared by the solid phase extraction. The calibration curves were linear over a concentration range of 0.5-200.0ng/mL for ddI and 0.25-100.0ng/mL for ddA-TP. The intra-day and inter-day precision was less than 15% and the relative error (RE) were all within ±15%. The validated method was successfully applied to assess the disposition characteristics of ddI and support cell pharmacokinetics after the patients with AIDS were orally administrated with ddI and tenofovir disoproxyl fumarate (TDF).
Department of Pharmacy, 94 Hospital of Nanjing Military Region, NO 1028 Jinggangshan street, Nanchang 330001, China.
Xu
X
Lan
Department of Pharmacy, Jiangxi Maternal and Child Health Hospital, NO 318 Bayi Road, Nanchang 330001, China.
Lei
L
Mingdao
Department of Pharmacy, Jiangxi University of Traditional Chinese Medicine, NO 818 Xingwan Road, Nanchang 330004, China.
Guo
G
Huilin
Department of Pharmacy, Jiangxi University of Traditional Chinese Medicine, NO 818 Xingwan Road, Nanchang 330004, China.
Gan
G
Wei
Department of Pharmacy, Jiangxi University of Traditional Chinese Medicine, NO 818 Xingwan Road, Nanchang 330004, China.
Hu
H
Lvjiang
Department of Infectious Diseases, The Ninth hospital of Nanchang, No. 167 South Hongdu Road, Nanchang 330002, China.
Zhou
Z
Yan
Department of Pharmacy, 94 Hospital of Nanjing Military Region, NO 1028 Jinggangshan street, Nanchang 330001, China. Electronic address: ligangnjnc@163.com.
Li
L
Gang
D000328:Adult; D019380:Anti-HIV Agents / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D003838:Deoxyadenine Nucleotides / Q000097:blood*; D016049:Didanosine / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use; D054306:Dideoxynucleotides / Q000097:blood*; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy; D006801:Humans; D057230:Limit of Detection; D008875:Middle Aged; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods*
D019380:Anti-HIV Agents; D003838:Deoxyadenine Nucleotides; D054306:Dideoxynucleotides; C037773:2',3'-dideoxyadenosine triphosphate; D016049:Didanosine
Cell pharmacokinetics; HPLC–MS/MS; Interaction; dA-TP; ddI