A near-infrared spectroscopic method to quantify drugs or excipients within polymeric matrixes is proposed. Cylindrical implants were fabricated by a melt-mold technique containing various ratios of poly(epsilon-caprolactone) (PCL) and poly(ethylene glycol) (PEG) and various loadings of lomefloxacin HCl with a constant ratio (70:30 w/w) of PCL/PEG. Near-infrared (NIR) spectra were obtained on intact sections of larger implants using a Foss NIRSystems Model 5000 monochrometer equipped with a Rapid Content Analyzer. Spectral data were treated with second derivative transformation followed by linear regression and PLS to obtain correlation with lomefloxacin or PEG content. Lomefloxacin content was separately determined by UV analysis (287 nm) using a validated extraction procedure. The NIR method was tested by comparing predicted loadings of test implants with either theoretical values based on weight (PEG) or with UV analysis results (lomefloxacin). Second derivative spectral values at particular wavelength ratios (PEG, 2064 nm/1698 nm; lomefloxacin, 2172 nm/2226 nm and 1824 nm/1862 nm) yielded linear results for PEG or lomefloxacin content. PEG content determined by NIR spectroscopy was in excellent agreement with theoretical content. Lomefloxacin content determined by NIR spectroscopy was also in excellent agreement with UV analysis. NIR analysis is interpreted through the use of corresponding mid-infrared spectral data.