Development and validation of esomeprazole magnesium trihydrate determination in workplace air using HPLC-MS/MS

Introduction. Esomeprazole is a proton pump inhibitor widely used in the treatment of acid-related diseases of the upper gastrointestinal tract. Upon inhalation exposure, it is classified as a substance of the highest hazard class, which requires monitoring its concentration in the workplace air at pharmaceutical enterprises. Despite the availability of methods for the quantitative analysis of esomeprazole in various matrices in the scientific literature, there are currently no methods for analyzing this substance in workplace or industrial air.

Aim. To develop a method for the quantitative determination of esomeprazole magnesium trihydrate in workplace air using HPLC-MS/MS.

Materials and methods. Air samples were collected using membrane filters with a diameter of 25 mm at a flow rate of 5,0 L/min. The analysis was performed using reference standards of esomeprazole magnesium trihydrate and carbamazepine. Chromatographic separation was carried out on a C18 column (2,5 μm, 100 × 4,6 mm). Detection was performed using a mass-selective detector in positive electrospray ionization mode by multiple reaction monitoring. MRM transitions were: 346,1 → 198,1 m/z for esomeprazole and 237,1 → 194,1 m/z for carbamazepine.

Results and discussion. The method was validated according to the following parameters: suitability of the chromatographic system (the number of theoretical plates, N, for esomeprazole is at least 13170 and for carbamazepine, at least 5617), the asymmetry factor (A_s) for both substances does not exceed 1,36 and 1,41, respectively; limit of detection: 17 ng/mL; lower limit of quantification: 50 ng/mL; specificity (the response of interfering peaks for esomeprazole at most 1,2 % and for carbamazepine at most 0,25 %); linearity in the range of 50–5000 ng/mL (determination coefficient (R₂) of at least 0,9995, accuracy from 92,8 to 106,1 %, and relative standard deviation (RSD, %) at most 4,2 %); intralaboratory accuracy (from 99,6 to 102,2 %) and interlaboratory accuracy (from 100,5 to 101,6 %); intralaboratory precision (RSD at most 4,3 %) and interlaboratory precision (RSD at most 5,8 %). All validation parameters met the acceptance criteria. The stability of esomeprazole on filters was confirmed for up to three months of storage.

Conclusion. The development and implementation of the method enabled quantitative analysis of esomeprazole in workplace air and the assessment of the safety of the production process in accordance with hygienic requirements.

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