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This is a Experimental Study study.

September 18, 2025

Development and Validation of a Highly Sensitive LC‐MS/MS Method for the Quantification of N‐Nitroso‐Desmethyl‐Zolmitriptan: A Nitrosamine Impurity in Zolmitriptan

RPRaja Venkata Prasad PathaJawaharlal Nehru Technological University, Hyderabad KDKarunakar DasaGovernment of Andhra Pradesh RBRama Devi BhoomireddyJawaharlal Nehru Technological University, Hyderabad

Key Points

The developed LC-MS/MS method achieves a limit of detection of 0.010 ppm for N-nitroso-desmethyl-zolmitriptan, demonstrating high sensitivity.
Method validation confirms excellent linearity over a concentration range of 0.032–3.95 ppm, with an R² value of 0.9975.
System suitability assessments yielded %RSD values of 1.0% for peak area, indicating method reliability and precision.
The optimized method is well-suited for routine quality control in pharmaceuticals, ensuring regulatory compliance and high recovery rates.

Abstract

ABSTRACT The study aimed to develop and validate a sensitive and robust LC‐MS/MS method for the quantification of N ‐nitroso‐desmethyl‐zolmitriptan in pharmaceutical samples, ensuring method specificity, accuracy, and regulatory compliance. Mass spectrometric parameters were optimized using an electrospray ionization (ESI) source in positive ion mode with multiple reaction monitoring (MRM). The precursor‐to‐product ion transitions were identified as Q1 m / z 303.10 with fragment ions at m / z 273.10, 230.0, and 144.0. Chromatographic separation was optimized using a Poroshell HPH C18 column (150 × 4.6 mm, 2.7 µm) with a mobile phase comprising 0.77 g of ammonium acetate in 1000 mL water with 0.3 mL formic acid (Mobile Phase A) and acetonitrile (Mobile Phase B). The method was validated in accordance with ICH guidelines, assessing system suitability, linearity, accuracy, precision, and sensitivity. System suitability parameters confirmed method consistency, with %RSD values of 1.0% for peak area and 1.9%–2.3% for bracketing standard injections. The method exhibited excellent linearity over a concentration range of 0.032–3.95 ppm with an R 2 value of 0.9975. Sensitivity assessment established the limit of detection (LOD) at 0.010 ppm and the limit of quantification (LOQ) at 0.032 ppm, with corresponding signal‐to‐noise ratios exceeding acceptance criteria. Accuracy studies demonstrated recovery rates of 92.4%–96.5% at the LOQ level and 96.1%–98.4% at 100% concentration. Precision at the LOQ level yielded a %RSD of 3.5%, confirming method reproducibility. The developed LC‐MS/MS method provides a reliable, specific, and sensitive approach for the quantification of N ‐nitroso‐desmethyl‐zolmitriptan in pharmaceutical matrices. The optimized chromatographic and mass spectrometric conditions ensured high recovery, precision, and linearity, making the method suitable for routine quality control and regulatory compliance in pharmaceutical analysis.

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