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<p>The purpose of this study was to study the trace-level quantification of carcinogenic N-nitroso-duloxetine as well as the residual duloxetine HCl in different reactor material cleaning solvent samples. Duloxetine is a serotonin–norepinephrine reuptake inhibitor with a secondary amine group in its structure, which makes it susceptible to nitrosation in the presence of nitrosating agents, favored by low pH conditions. The sensitive LC–HRMS method was developed using an Agilent Poroshell C18 column with an isocratic elution (0.1% formic acid (FA) in water:0.1% FA in methanol: 20:80 v/v) with heated electrospray ionization as the ionization source coupled with Q-Orbitrap, and was also monitored at 298.1260&#xa0;<i>m</i>/<i>z</i> for DXT and 349.0981&#xa0;<i>m</i>/<i>z</i> for NDXT. The different reactor materials were selected for the recovery study. The developed method confirmed excellent linearity from 3 to 1000&#xa0;ppb over the concentration range, with correlation coefficients of 0.9997 (DXT) and 0.9995 (NDXT), an LOD of 3&#xa0;ppb, and an LOQ of 10&#xa0;ppb. The recovery range of the method was from 71.5% to 95.6% in different reactor materials. The precision indicated by %RSD ranged from 0.7% to 5.6%. The robustness range was within 2.0%, confirming that the method is robust and reliable. The formation of NDXT from DXT has been studied, revealing significant NDXT formation from DXT at pH 2.5, 3.0, 5.0, and 7.3 in the presence of nitrite. This method facilitates the detection of NDXT and DXT in pharmaceutical manufacturing reactor cleaning samples and achieves an AGREE score of 0.75, reflecting its strong environmental friendliness through minimal sample use and reduced waste.</p>

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Simultaneous Determination of Duloxetine and N-Nitroso-Duloxetine in Reactor Cleaning Solvent Samples by LC–HRMS: Formation, Quantitation, and Green Assessment

  • 期刊论文

  • 发表日期：

    2026年4月27日

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  • Nagaraju Rajana,
  • Gayatri Gajanan Kulkarni

摘要

The purpose of this study was to study the trace-level quantification of carcinogenic N-nitroso-duloxetine as well as the residual duloxetine HCl in different reactor material cleaning solvent samples. Duloxetine is a serotonin–norepinephrine reuptake inhibitor with a secondary amine group in its structure, which makes it susceptible to nitrosation in the presence of nitrosating agents, favored by low pH conditions. The sensitive LC–HRMS method was developed using an Agilent Poroshell C18 column with an isocratic elution (0.1% formic acid (FA) in water:0.1% FA in methanol: 20:80 v/v) with heated electrospray ionization as the ionization source coupled with Q-Orbitrap, and was also monitored at 298.1260 m/z for DXT and 349.0981 m/z for NDXT. The different reactor materials were selected for the recovery study. The developed method confirmed excellent linearity from 3 to 1000 ppb over the concentration range, with correlation coefficients of 0.9997 (DXT) and 0.9995 (NDXT), an LOD of 3 ppb, and an LOQ of 10 ppb. The recovery range of the method was from 71.5% to 95.6% in different reactor materials. The precision indicated by %RSD ranged from 0.7% to 5.6%. The robustness range was within 2.0%, confirming that the method is robust and reliable. The formation of NDXT from DXT has been studied, revealing significant NDXT formation from DXT at pH 2.5, 3.0, 5.0, and 7.3 in the presence of nitrite. This method facilitates the detection of NDXT and DXT in pharmaceutical manufacturing reactor cleaning samples and achieves an AGREE score of 0.75, reflecting its strong environmental friendliness through minimal sample use and reduced waste.