Here, we describe a combination approach using Two Calibration-Free Methods with reflectance near-infrared (TCFM-NIR), which involves detecting end-points for active pharmaceutical ingredients (APIs) blending by simultaneously monitoring specific NIR peak intensity of APIs and calculating moving block standard deviation (MBSD). After determining the specific NIR peak range of nicaldipine hydrochloride, conditions for TCFM-NIR were established by monitoring the differential intensity of the second peak (1136 nm) while MBSD was calculated from the NIR peak intensity between 1100 and 1150 nm. In comparison with the validated reference method of UV-VIS spectroscopy, which is particularly destructive. TCFM-NIR was found to be useful in detecting end-points for blending of nicaldipine hydrochloride. TCFM-NIR monitors two important factors for estimation of blend uniformity: API concentration, using specific NIR peak intensity for APIs, and blend homogeneity, using MBSD. Also, the conditions of TCFM-NIR were confirmed to be adequate by using Partial Least Square (PLS). Further, simultaneously monitoring these two blend uniformity factors is more useful in preventing estimation errors for nondestructive monitoring of blend homogeneity than monitoring only one factor, as with NIR spectroscopy. (C) 2011 Elsevier B.V. All rights reserved.