Microextraction by packed sorbent of N‐nitrosamines from Losartan tablets using a high‐throughput robot platform followed by liquid chromatography‐tandem mass spectrometry

Abstract

The development of a fast, cost-effective, and efficient microextraction by packed sorbent setup was achieved by combining affordable laboratory-repackable devices of microextraction with a high-throughput cartesian robot. This setup was evaluated for the development of an analytical method to determine Nnitrosamines in losartan tablets. N-nitrosamines pose a significant concern in the pharmaceutical market due to their carcinogenic risk, necessitating their control and quantification in pharmaceutical products. The parameters influencing the performance of this sample preparation for N-nitrosamines were investigated through both univariate and multivariate experiments. Microextractions were performed using just 5.0 mg of carboxylic acid-modified polystyrene divinylbenzene copolymer as the extraction phase. Under the optimized conditions, the automated setup enabled the simultaneous treatment of six samples in less than 20 min, providing reliable analytical confidence for the proposed application. The analytical performance of the automated high-throughput microextraction by the packed sorbent method was evaluated using a matrix-matching calibration. Quantification was performed using ultra-high-performance liquid chromatography-tandem mass spectrometry with chemical ionization at atmospheric pressure. The method exhibited limits of detection as low as 50 ng/g, good linearity, and satisfactory intra-day (1.38-18.76) and inter-day (2.66-20.08) precision. Additionally, the method showed accuracy ranging from 80% to 136% for these impurities in pharmaceutical formulations.

Development of a reliable method for determination of N-nitrosamines in medicines using disposable pipette extraction and HPLC-MS analysis

“…This is not efficient for extracting NAs from an aqueous medium, consistent with findings reported in the literature. 13 Furthermore, the HLB phase, widely used for NA extraction, 12 did not demonstrate great recovery results as well, and this result may be related to the sorbent behavior in the DPX extraction procedure. The HLB phase, compared to the other phases evaluated here, exhibits a smaller particle size, which increases the contact surface area and may lead to higher recoveries.…”

“…15 The literature presents solvents such as dichloromethane and acetonitrile for NA extraction. 13,26 In this study, acetonitrile, methanol and isopropanol were evaluated as desorption solvents, which exhibit moderate polarity, similar to these analytes and are compatible solvents with the HPLC-MS system. In this step, the C18 extraction phase was employed, with 2 cycles of extraction and desorption, and a 10 second equilibration time in each extraction cycle, and the sample pH remaining unaltered.…”

“…Furthermore, the absence of a sample preparation step may contribute to undesired effects in the analysis, such as matrix effects and carryover. 12–14…”