A simple spectrophotometric method for the determination of N-acetyl-L-cysteine (NAC) and N-(2-mercaptopropionyl)glycine (MPG) in pharmaceutical preparations was developed, validated, and used. The proposed equilibrium method is based on a coupled two-step redox and complexation reaction. In the first step, Fe(III) is reduced to Fe(II) by NAC or MPG. Subsequently, Fe(II) is complexed with 2,4,6-tripyridyl-s-triazine (TPTZ). Several analytical parameters of the method were optimized for NAC and MPG analysis in the concentration range from 1.0？μM to 100.0？μM. Regression analysis of the calibration data showed a good correlation coefficient (0.9999). The detection limit of the method was 0.14？μM for NAC and 0.13？μM for MPG. The method was successfully applied to quantify NAC and MPG in pharmaceutical preparations. No interferences were observed from common pharmaceutical excipients. 1. Introduction N-Acetyl-L-cysteine (NAC) is an endogenous aminothiol present both in human plasma and in urine [1]. N-(2-Mercaptopropionyl)glycine (MPG), also known as tiopronin, is a synthetic aminothiol antioxidant. NAC has been in clinical use for more than 40 years, primarily as a mucolytic agent in a variety of respiratory illness. Intravenous and oral administration of NAC have been extensively used in the management of paracetamol (acetaminophen) poisoning [1]. MPG is primarily used in the treatment of cystinuria [2], but studies have shown that MPG can be used as a chelating, cardioprotecting, and radioprotecting agent [3], as well as an antidote to heavy metal poisoning [4]. A number of electrochemical [5–9], fluorometric [10–12], chemiluminescence [13–15], and liquid chromatographic [16–18] methods have been developed for the determination of NAC and MPG in biological samples and pharmaceuticals. Some of these methods are in part time consuming or require expensive equipment. Other published methods suffer from lack of selectivity and sensitivity. Spectrophotometry is the most widely used technique in pharmaceutical analysis because it is simple, economic, and easily available to most quality control laboratories. Spectrophotometric methods have also been reported for the determination of NAC and MPG in pharmaceutical formulations [19–25]. A coupled redox-complexation reaction has been reported for the spectrophotometric analysis of NAC and MPG using 1,10-phenanthroline as the chromogenic reagent [24]. In the present work, we report a simple and cost-effective spectrophotometric method for the reliable analysis of NAC and MPG in pharmaceutical formulations. The
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