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. 2017 Feb 15:1044-1045:70-76.
doi: 10.1016/j.jchromb.2016.12.031. Epub 2016 Dec 30.

HPLC-UV method for simultaneous determination of MK-1775 and AZD-7762 in both acetonitrile-aqueous solution and mouse plasma

Kareem Ebeid  1 , Giang N Ho  1 , Aliasger K Salem  2
Affiliations

HPLC-UV method for simultaneous determination of MK-1775 and AZD-7762 in both acetonitrile-aqueous solution and mouse plasma

Kareem Ebeid et al. J Chromatogr B Analyt Technol Biomed Life Sci. .

Abstract

A sensitive and precise method is described for the simultaneous determination of two small molecule kinase inhibitors: MK-1775 (MK) and AZD-7762 (AZD), in acetonitrile (ACN)-aqueous solution and in mouse plasma. A Nova-Pak C18 reversed phase column (3.9mm×150mm, 4μm, 60Å) was utilized in the separation using an isocratic mobile phase of 0.1% v/v triethylamine in phosphate buffer (pH=7.4): acetonitrile (ACN) (60:40, v/v), at a flow rate of 0.8mL/min. Detection wavelength was set at 310nm for both MK and AZD, and 431nm for the internal standard sunitinib (SUN). The developed method was validated following the ICH guidelines and it was shown to be accurate, precise and linear in the range of 41ng/mL to 8333ng/mL for both drugs in the ACN-aqueous solution and from 83ng/mL to 8333ng/mL for both drugs in mouse plasma samples. For the first time, the presented data suggest the suitability of this method for the simultaneous separation and quantification of MK and AZD in both ACN aqueous solution as well as in mouse plasma samples.

Keywords: AZD-7762; HPLC-UV; MK-1775; Mouse plasma; Solid phase extraction; Sunitinib.

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Figures

Figure 1
Figure 1. UV spectrums and chemical structures of MK, AZD and SUN
Figure 2
Figure 2
Representative chromatogram at 310 and 431 nm. (a) 1 μg/mL MK in ACN-aqueous solution (5.50 min), (b) 1 μg/mL AZD in ACN-aqueous solution (14.02 min), (c) 2 μg/mL SUN in ACN-aqueous solution (21.50 min), (d) Mixture of MK, AZD and SUN in ACN-aqueous solution, (e) Blank plasma sample after extraction, (f) Mixture of MK, AZD and SUN after plasma extraction.
Figure 3
Figure 3
Calibration curve of MK and AZD in ACN-aqueous solution and in mouse plasma.
See this image and copyright information in PMC

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