Quantitative plasma determination of a novel antiretroviral derivative of zidovudine by solid-phase extraction and high-performance liquid chromatography

Abstract

A solid-phase extraction methodology, followed by high-performance liquid chromatography (HPLC) quantification with UV absorbance detection (lambda = 267 nm), was developed in order to study the stability of 3'-azido-3'-deoxy-5'-O-isonicotinoylthymidine (AZT-Iso), a novel derivative of the antiretroviral AZT, in different matrixes. The half-lives (t1/2) for AZT-Iso were 1.19, 1.13 and 0.30 h for human, rat and rabbit plasma, respectively, and 14.91 and 25.49 h for potassium phosphate buffer (pH 7.4) and human serum albumin solution, respectively. The HPLC method proved to be selective, sensitive and accurate. Good recovery, linearity and precision were achieved using p-fluorophenol as an internal standard. The validity of this method was tested using synthetic mixtures of the intact drug with its decomposition products. In conclusion, the method presented is applicable to in vivo pharmacokinetics studies of AZT-Iso in rats.

Nucleoside reverse transcriptase inhibitors and their phosphorylated metabolites in human immunodeficiency virus-infected human matrices

“…Wiesner et al used the same SPE cartridge to extract d4T in plasma with the mean recovery of 94% [41]. Quevedo et al also applied the similar extraction cartridges containing 500 mg of RP silica to extract 3 -azido-3 -deoxy-5 -Oisonicotinoylthymidine (AZT-Iso) that is a novel derivative of the antiretroviral AZT in human, rat and rabbit plasma samples with the recoveries of between 93.1 and 99.4% [42].…”

“…Quevedo et al presented a HPLC method for the quantification of 3 -azido-3 -deoxy-5 -Oisonicotinoylthymidine (AZT-Iso) in rat plasma with UV detection. The method was proved to be selective, sensitive and accurate [42]. Marchei et al suggested a simple RP-HPLC method with UV detection at 265 nm for the simultaneous determination of AZT and nevirapine in human plasma [58].…”

Determination of the Antiretroviral Drug Zidovudine in Diluted Alkaline Electrolyte by Adsorptive Stripping Voltammetry at the Mercury Film Electrode

“…Several methods have been discovered for the quantitative determination of zidovudine including chromatog- raphy [9][10][11][12][13][14][15], fluorescence polarization immunoassay [16], using diamond paste based immunosensor [17], fluorescence spectroscopy [18] and voltammetry [19][20][21][22][23][24].…”

Formulation, In Vitro and In Vivo Pharmacokinetics of Anti-HIV Vaginal Bioadhesive Gel

“…About 1 mL plasma was mixed with 1 mL of 15 w/v% trichloro acidic acid (TCA), shaken well for 3 min and centrifuged at 3000rpm for 15 min. The plasma samples were analyzed for AZT by first passing the plasma samples through Silica gel column and analyzed by HPLC (LC-20 AT, Shimadzu, Japan) using mobile phase methanol:water (60:40)[19] at a flow rate of 1.2 mL/min. Twenty microliters of injection volume was eluted in RP C(18) column (4.6 mm × 150 mm) at room temperature.…”