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. 2017 Aug 28:12:1177390117726776.
doi: 10.1177/1177390117726776. eCollection 2017.

Quality by Design-Applied Liquid Chromatography-Tandem Mass Spectrometry Determination of Enzalutamide Anti-Prostate Cancer Therapy Drug in Spiked Plasma Samples

Ask Sankar  1   2 , Shanmugasundaram Palani  3 , Ravichandiran Velayudham  4
Affiliations

Quality by Design-Applied Liquid Chromatography-Tandem Mass Spectrometry Determination of Enzalutamide Anti-Prostate Cancer Therapy Drug in Spiked Plasma Samples

Ask Sankar et al. Anal Chem Insights. .

Abstract

This research article presents the Quality by Design (QbD)-finalised conditions for a method that uses liquid chromatography-tandem mass spectrometry for the determination of concentration of enzalutamide (ENZ), an atypical anticancer drug, in a drug formulation and in spiked plasma samples. Critical process attributes (CPA) considered to be the influential parameters in separation, identification, and quantification processes by ultrahigh-performance liquid chromatography-electrospray ionisation-tandem mass spectrometry (UHPLC-ESI-MS/MS) were organic content, buffer strength, pH modifier, flow rate, spray voltage, sheath gas, and auxiliary gas that alter critical analytical attributes, such as retention time (R1) and area (R2). These factors were evaluated first in a factorial design (Taguchi orthogonal array design) and then extensively in a central composite design (CCD) to zero-in on the mobile phase for the quantification of ENZ standard drug and along with its internal standard (ENZIS) in spiked plasma samples and in formulation. Pareto chart from initial factorial design (Taguchi orthogonal array design) model suggested which of the CPA factors should be given the weightage, that is, to be exhaustively analysed in the CCD and response surface analysis. The elaborated parameters proposed by World Health Organization were studied by method validation, ie, selectivity, linearity, accuracy, precision repeatability system-suitability tests, method robustness/ruggedness, sensitivity, and stability. The strategy followed gives an insight on the development of a robust QbD-compliant quantitative UHPLC-ESI-MS/MS method for ENZ drug containing plasma samples (spiked).

Keywords: Enzalutamide; Quality by Design; UHPLC-ESI-MS/MS; anti-prostate cancer; response surface analysis; spiked plasma samples.

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Conflict of interest statement

Declaration of conflicting interests:The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
Structure of ENZ (enzalutamide).
Figure 2.
Figure 2.
A Pareto chart showing effects of influential critical process attributes on first response, Rt (retention time).
Figure 3.
Figure 3.
Perturbation plot showing the factors influence on Rt (retention time).
Figure 4.
Figure 4.
A Pareto chart showing effects of influential CPA on second response, area.
Figure 5.
Figure 5.
Perturbation plot showing the factors influence on area.
Figure 6.
Figure 6.
Response surface plot showing the desirability for the selected factors.
Figure 7.
Figure 7.
Response surface plot showing the effects of selected factors on Rt (retention time).
Figure 8.
Figure 8.
Response surface plot showing the effects of selected factors on area.
Figure 9.
Figure 9.
Representative chromatogram of the enzalutamide in the predicted settings.
Figure 10.
Figure 10.
Linearity fit of the ratio of area of ENZ and ENZIS. ENZ indicates enzalutamide; ENZIS enzalutamide with internal standard.
See this image and copyright information in PMC

References

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