A novel green HS/SPME-GC/NPD method for screening and quantification of nitrosamines in solid samples: Application to losartan tablets.

Abstract

The presence of nitrosamines (NAs) in pharmaceutical products represents a significant risk to patient health and can compromise the quality of products during manufacturing processes. This study proposes a direct analysis method for solid samples of losartan tablets to determine the presence of six NAs using headspace solid-phase microextraction (HS/SPME) coupled with gas chromatography and nitrogen-phosphorus detection (GC/NPD). This method provides a green, low-cost approach for screening and quantification in quality control laboratories. A DVB/Car/PDMS fiber was employed for extraction under optimized conditions, which included the analysis of four tablets, agitation at 250 rpm, an extraction time of 85 min, and a temperature of 45 °C. The performance of the method was evaluated, showing determination coefficients greater than 0.99 through solid-spiking matrix-matched calibration, with detection limits ranging from 0.0001 to 0.0157 mg kg^-1, recovery rates between 79.7 % and 122.0 %, and precision values below 18.7 %. The validation parameters demonstrated excellent selectivity and sensitivity, confirming the efficacy of the method in identifying and quantifying mutagenic compounds in compliance with pharmaceutical regulatory guidelines. Among the thirteen tablets analyzed, two contained NDEA at levels exceeding regulatory limits, highlighting the effectiveness of the method. The environmental sustainability of the method was assessed using the Analytical GREEnness (AGREE) calculator, which confirmed its alignment with Green Chemistry principles. Moreover, this approach is applicable to other solid samples, including pure active pharmaceutical ingredients and finished pharmaceutical products.