A novel chemiluminescence method using β − cyclodextrins coated on CoFe2O4 magnetic nanoparticles is proposed for the chemiluminometric determination of montelukast in plasma. The effect of coated β − cyclodexterinon CoFe2O4 magnetic nanoparticles in the chemiluminescence of luminol–H2O2 system was investigated. It was found that β − cyclodexterin coated on CoFe2O4 magnetic nanoparticles could greatly enhance the chemiluminescence of the luminol–H2O2 system. Doehlert design was applied in order to optimize the number of experiments to be carried out to ascertain the possible interactions between the parameters and their effects on the chemiluminescence emission intensity. This design was selected because the levels of each variable may vary in a very efficient way with few experiments. Doehlert design and response surface methodology have been employed for optimization pH and concentrations of the components. Results showed under the optimized experimental conditions, the relative CL intensity (ΔI) is increased linearly in the concentration range of 0.003–0.586 μgml−1 of montelukast with limit of detection (LOD) 1.09 × 10−4 μgml−1 at S/N ratio of 3, limit of quantitative (LOQ) 3.59 × 10−4 μgml−1 and the relative standard deviation 2 .63 %. The method has been successfully applied to the determination of montelukast in plasma of human body. Results specified that relative chemiluminescence intensity (ΔI) has good proportional with the montelukast concentration with R2 = 0.99979. The test of the recovery efficiency for known amounts of montelukast was also performed, the recoveries range obtained from 98.2 to 103.3 %, with RSDs of <4 % indicated that the proposed method was reliabl
