HPLC-MS/MS quantification of the HIV-1 protease inhibitor saquinavir in mice plasma and brain

doi:10.5246/jcps.2017.02.009

Abstract

Abstract:

In the present study, a rapid and sensitive liquid chromatography-tandem mass spectrometric method for the determination of saquinavir in mice plasma and brain was developed, validated, and applied to a preliminary screening study evaluating the effect of bioflavonoids on the brain distribution of saquinavir in mice. Saquinavir and the internal standard (ritonavir) were isolatedfrom plasma and homogenized brain tissue matrices using a liquid-liquid extraction procedure, and the chromatographic separationwas accomplished by using a reversed phase C₁₈column (150 mm×2.1 mm, 5.0 μm). The analyte was detected by a triple-quadrupole tandem mass spectrometer via electrospray ionization, and multiple reaction monitoring was employed to select both saquinavir and ritonavir in the positive ion mode. A linear dynamic range of 0.1-10 ng/mL for plasma samples was established and the lower limit of quantification was 0.1 ng/mL. The intra- and inter-day precision were 7.5%-12.1%, and the accuracies ranged from 90.5% to 107.2% for plasma. A linear dynamic range of 0.1-10 ng/g for brain samples was established and the lower limit of quantification was 0.1 ng/g. The intra- and inter-day precision were 7.3%-11.9%, and the accuracies ranged from 90.8% to 107.4% for brain tissue samples. This method was successfully applied a preliminary screen of 19 bioflavonoids on the brain distribution of saquinavir in mice, and biochanin A shows the strongest effect.

Key words: Saquinavir, HPLC-MS/MS, Flavonoids, Brain

CLC Number:

R917

Supporting:

Gongwen Liang, Na Li, Liping Ma, Libo Zhao, Luwen Shi. HPLC-MS/MS quantification of the HIV-1 protease inhibitor saquinavir in mice plasma and brain[J]. Journal of Chinese Pharmaceutical Sciences, 2017, 26(2): 106-114.

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