A flow injection chemiluminescent (FI-CL) method has been developed for the simultaneous determination of codeine and noscapine using N-PLS regression. The method is based on the fact that kinetic characteristics of codeine and noscapine are different in the Ru(phen)(3)(2+)-Ce(IV) CL system. In flow injection mode, codeine gives broad peak with the highest CL intensity at 4.4s, whereas the maximum CL intensity of the noscapine appears at about 2.6s. Moreover, the effect of increasing H(2)SO(4) concentration was different on the CL intensity of the compounds. An experimental design, central composite design (CCD), was used to realize the optimized variables such as Ru(II) and Ce(IV) concentrations for the both compounds. At the optimized condition, a three-way data structure (samples, H(2)SO(4) concentration, time) was constructed and followed by N-PLS regression. The number of factors for the N-PLS regression was selected based on the minimum values for the root mean squared error of cross validation (RMSECV). The proposed method is applied to the simultaneous quantification of codeine and noscapine in the pharmaceutical preparations.