Simultaneous determination of drugs in concentration ratios above 40:1 by application of multivariate calibration to absorbance and derivative spectrophotometric signals

The performance of two multivariate calibration methods, multiple linear regression (MULTI3) and partial least-square regression (PLS-2), for the resolution of the ternary mixtures of acetylsalicylic acid-caffeine-codeine and acetaminophen-caffeine-codeine is compared. The methodologies were checked by applying them to the analysis of two sets of laboratory-prepared mixtures over the concentration ranges 13.0–19.0, 1.00–3.00 and 0.20–1.00 μg · ml−1 for acetylsalicylic acid-caffeine-codeine and 12.0–22.0, 0.40–2.00 and 0.20–1.00 μg · ml−1 for acetamimophen-caffeine-codeine, respectively. While the results provided by MULTI3 were unacceptable in the majority of the cases, those obtained by PLS-2 were quite good with considerably diminished errors, as a result of calibration and/or checking with MULTI3, taking no account of potential interactions between analytes. It was shown that it is possible by using PLS-2 to resolve complex mixtures of analytes in a highly disparate proportion, even when they have overlapping signals. The proposed method was successfully demonstrated for pharmaceutical tablets.