*Sigma Pharmaceutical Industries, Quesna, Egypt, **Department of Analytical Chemistry, Faculty of Pharmacy, Zagazig University, Egypt Email: Original Article COMPARISON OF FT-NIR TRANSMISSION AND HPLC FOR GREEN APPROACH TO DETERMINE PARACETAMOL AND ITS DEGRADATION PRODUCT 4-AMINOPHENOL IN PARACETAMOL TABLETS AHMED BADR ELDIN*, OMNIA AHMED ISMAIEL**, WAFFA HASSAN**, ABDALLA SHALABY** a.badr@sigma-pharm.com Received: 04 May 2015 Revised and Accepted: 01 Jun 2015 ABSTRACT Objective: Development and validation of Near infrared (NIR) spectroscopic method for determination of paracetamol and its major degradation product 4-aminophenol in paracetamol tablets and show the agreement between the NIR as a greener technique and the conventional high performance liquid chromatography (HPLC) method, official in British pharmacopeia (BP). Methods: Calibration model for paracetamol and its degradation product 4-aminophenol was built by utilizing chemometric processing which is the most critical step in the development of specific and robust NIR models. It is based mainly on a partial least square regression fit on the transmission mode using paracetamol, 4-aminophenol and excipient materials of the drug products. The results obtained by NIR spectroscopy were compared with the compendial HPLC method in the BP. Results: The chosen models had a root mean square error of the cross validation (RMSECV) values of 1.38, 1.42 and coefficient of correlation (r2) of 99.1, 99.05 for paracetamol and 4-aminophenol respectively, which indicates good fitness and accuracy of the model. Conclusion: The present study showed that NIR could be used with high accuracy for determination of for parent drug and its major degradation product in paracetamol tablets. This proposed technique realizes many of green analytical aspects in developing eco-friendly analytical methods and may replace safely the conventional chromatographic technique without compromising efficacy. Keywords: Paracetamol, 4-Amino phenol, FT-NIR transmission, GAC (green analytical chemistry), HPLC assay, Validation, PLS model. INTRODUCTION The trend of sustainable development requires chemistry to be “clean” or “green.” In the 1990s, therefore, the concept of “Green Chemistry” was proposed, together with the “Twelve Principles of Green Chemistry.”Presently, spectroscopic methods dominate the area of green analytical chemistry [1]. The pursuit in the field of green chemistry is growing dramatically and is becoming a grand challenge for chemists to develop new products, processes and services that achieve the necessary social, economic and environmental objectives due to an increased cognizance of environmental safety, checking environmental pollution, sustainable industrial ecology and cleaner production technologies worldwide [1]. The NIR region spans the wavelength range 12,500–4000 cm -1 Paracetamol is an old molecules, it is a synthetic non-opiate derivative of 4-aminophenol. Several methods for determination of the drug and its main degradation product have been reported such as spectrophotometric in dosage form [ . In this region, absorption bands correspond mainly to overtones and combinations of fundamental vibrations [2]. In the pharmaceutical sector, several qualitative and quantitative applications of NIR spectroscopy have been described during the manufacturing steps. At the beginning of the manufacturing process, NIR can be used for the identification of active substances and excipients [3–5]. 6, 7], fluorimetric in raw material and dosage forms [8], voltammetric in dosage forms and biological fluids [9], high-performance liquid chromatography [10– 12], chemiluminescence [13, 14] and capillary electrophoresis [15] methods. However, using NIR for determination of paracetamol has been reported, but using this technique for simultaneous determination of the drug and its parent molecule is a quite new approach. The aim of this study is to show the agreement between the NIR as a greener technique and the conventional HPLC–UV detection method, official in British pharmacopeia. MATERIALS AND METHODS Materials All materials were supplied by SIGMA pharmaceuticals Corp., Egypt. The commercial samples of paracetamol 500 mg tablets were used and a placebo contains the same raw materials used in the production process, including microcrystalline cellulose, starch, sodium starch glycolate, polyvinylpyrrolidone, magnesium stearate and purified talc. The placebo was used to make serials of dilutions for establishing the calibration model. All materials are of pharmaceutical grade and all chemicals and reagents have been used in the HPLC method are analytical reagent of HPLC grade. NIR spectroscopy FT-NIR Spectrometer, MPA Flexible from Bruker Optics (Germany) was used. Pistol grip model with external trigger and LED status lights. It is equipped with two fiber optic probes, NIR probe for liquids "quartz" and NIR probe for solid. Includes 2 m fiber optic cable with Bruker quick connect. Fixed optical path length of 1 mm. NIR probe for solids, probe head length 80 mm, mounting of an integrating sphere for analysis of solid samples in diffuse reflectance and a measurement unit for analyzing highly scattering solid media in transmission. The spectrometer is equipped with a fast, PC-based data system with OPUS/IR FT-IR spectroscopy software package (version 5.0), which was provided by Bruker Optics. OPUS IDENT is a software package designed to identify substances by their NIR spectra while OPUS Quant is designed for the quantitative analysis. For this purpose, OPUS QUANT was used with a partial least square (PLS) fit method. In PLS, the calibration involves correlating the data in the spectral matrix X with the data in the concentration matrix Y. This means that the factoring of the spectral data is more suited for concentration prediction. Constructing the PLS model In a first step a PLS regression model was built using calibration samples. The obtained model was chemo metrically validated by International Journal of Pharmacy and Pharmaceutical Sciences ISSN- 0975-1491 Vol 7, Issue 7, 2015 Innovare Academic Sciences