This paper describes the three multipurpose methods for simultaneous estimation of Ambroxol Hydrochloride (AMB) , Guaiphensin (GUA), Cetirizine Hydrochloride (CET) and Phenylephirine (PHE) whether they were present in binary combination of any two drugs, tertiary combination of any three drugs or quaternary combination of all four drugs. Such methods were developed through applying chemometrics and also called multivariate analysis. The calibration model of 36 composite mixtures were prepared and three methods named Classical Least Square (CLS), Inverse Least Square (ILS), Principle Component Regression (PCR) has been developed and cross validated with mean recoveries of 101.4%, 100.8 % ,99.6%,99.9% for AMB , GUA, CET and PHE. A different validation set was also formed to estimate figure of merits which are Limit Of Quantification (LOQ), found to be 2.9 �µg/mL, 3.2 �µg/mL, 1.4 �µg/mL and 6.3 �µg/mL for AMB, GUA, CET and PHE, Limit of Detection (LOD) was 1.01 �µg/mL, 1.07 �µg/mL, 0.48 �µg/mL and 2.11 �µg/mL for AMB, GUA CET, and PHE. The model was then applied to 6 different market combinations in binary, tertiary or quaternary forms, the statistics were applied to conclude that there is no significant difference between the methods. The accepted t-value (less than 5.42) of marketed samples confirms that these all methods are suitable for routine assay of selected drugs in binary/ tertiary or quaternary combination.
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