A HPLC method for simultaneous determination of 5-aminoimidazole-4-carboxamide riboside and its active metabolite 5-aminoimidazole-4-carboxamide ribotide in tumor-bearing nude mice plasma and its application to pharmacokinetics study.

Abstract

A HPLC method with on-line solid phase extraction (SPE) and column switching was developed for simultaneous determination of 5-aminoimidazole-4-carboxamide riboside (AICA riboside) and its active metabolite 5-aminoimidazole-4-carboxamide ribotide (AICA ribotide) in nude mice plasma. Plasma sample was deproteinized by adding a half volume of 10% trichloroacetic acid (TCA), and the resulting supernatant was extracted with diethyl ether to remove TCA. 50 μl aqueous fraction was injected onto a WAX-1 SPE column, and AICA ribotide was trapped on the SPE column, while AICA riboside was eluted from the SPE column. The chromatographic separation of AICA riboside was achieved on CG16 column, and separation of AICA ribotide was performed on HILIC-10 and WAX-1 column. The columns temperature was maintained at 40 °C, and the optimal detection wavelength was 268 nm for both AICA riboside and AICA ribotide. The total analytical run time was 40 min. The proposed method was linear over the range of 0.1-500 μg/ml for AICA riboside and 0.03-50 μg/ml for AICA ribotide. The lower limit of quantification (LLOQ) was 100 and 30 ng/ml for AICA riboside and AICA ribotide, respectively. The sensitivity, accuracy and precision of this method were within acceptable limits during validation period. The method was successfully applied to investigate the pharmacokinetics characteristics of AICA riboside and its active metabolite AICA ribotide in nude mice bearing MCF-7 cell xenografts.

• Authors: Xiaoliang Cheng, Liping Guo, Zaiquan Li, Liang Li, Tianyan Zhou, Wei Lu
• Journal: Journal of chromatography. B, Analytical technologies in the biomedical and life sciences (J Chromatogr B Analyt Technol Biomed Life Sci) Vol. 915-916 Pg. 64-70 (Feb 01 2013) ISSN: 1873-376X [Electronic] Netherlands
• PMID: 23340307 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier B.V. All rights reserved.

Chemical References

• Ribonucleosides
• Ribonucleotides
• Aminoimidazole Carboxamide
• acadesine
• AICA ribonucleotide

Topics

• Aminoimidazole Carboxamide (analogs & derivatives, blood, chemistry, pharmacokinetics)
• Animals
• Chromatography, High Pressure Liquid (methods)
• Drug Stability
• Female
• Humans
• Linear Models
• MCF-7 Cells
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Reproducibility of Results
• Ribonucleosides (blood, chemistry, pharmacokinetics)
• Ribonucleotides (blood, chemistry, pharmacokinetics)
• Sensitivity and Specificity
• Solid Phase Extraction (methods)
• Temperature
• Transplantation, Heterologous