Development and validation of a method for the quantitative determination of metoprolol succinate in the air of the working area by high-performance liquid chromatography using mass spectra

Introduction. Metoprolol is a cardioselective blocker of β-adrenergic receptors. Drugs containing metoprolol have hypotensive, antianginal, antiarrhythmic effects. Moderately dangerous when taken orally, has a general toxic effect. Metoprolol is produced in two forms: in the form of salts of tartaric and succinic acids, the approximate safe level of exposure to which is 0.3 mg/m³. To ensure the safety of workers, it is necessary to carry out sanitary and hygienic air control. Methods for the quantitative analysis of metoprolol in the air of the working area, presented in the current scientific literature, allow monitoring only for metoprolol salts in the form of tartrate.

The aim of the study is to develop and validate an analytical method for the quantitative determination
of metoprolol succinate in the air of the working area by HPLC-MS.

Materials and methods. For the analysis, standard samples of metoprolol succinate and air samples taken at all stages of the life cycle of the production of the drug metoproolol were used. Chromatographic separation and detection were performed on an Agilent 1260 Infinity G6125B high performance liquid chromatograph (Agilent Technologies, USA) equipped with a column and sample thermostat, a degasser, a pump, an autosampler, and a G6125B mass selective detector. A Waters Xbridge^® C18 3.5 µm column was used; 2.1×30 mm (Waters, Ireland). Primary data were processed using Open Lab CDS ChemStation Edition (Rev. C.01.07 SR3) software (Agilent Technologies, USA).

Results. A method for the quantitative determination of metoprolol succinate in air samples by HPLC-MS has been developed and validated. During the validation of the developed methodology, it was found that the validation characteristics (specificity, linearity, accuracy and precision, correctness, reproducibility) are within the acceptance criteria. The analytical range of the technique was 0.1–10.0 µg/ml and allows the developed technique to be used to control the average shift MPCs in the air of the working area.

Limitations. The results of the study of the air in the working area are applicable only to the production of the drug metoprolol in the form of tablets; the study of air during the synthesis and packaging of the active pharmaceutical substance was not carried out.

Conclusion. An analysis of air samples from the production of the drug metoprolol was carried out and the safety of working conditions was proved.

Compliance with ethical standards. This study does not require the conclusion of a biomedical ethics committee or other documents.

Contribution of authors:
Savchenko A.Yu. — concept and design of the study;
Kartamyshev I.I. — the concept and design of the study, writing the text, editing, collection and processing material, statistical analysis;
Zhiltcov P.A., Dubovik N.S. — writing the text, collecting literature data.
All co-authors — approval of the final version of the article, responsibility for the integrity of all parts of the article.

Conflict of interest. The authors declare no conflict of interest.

Acknowledgments. The study was funded by AstraZeneca Industries LLC.

Received: December 12, 2023 / Accepted: December 28, 2023 / Published: February  29, 2024

1. Nebieridze D.V. Topical issues of the use of beta-blockers in clinical practice. Arterial’naya gipertenziya. 2009; 15(4): 413. (in Russian)

2. Shapovalova E.N., Pirogov A.V. Chromatographic methods of analysis: Methodological guide for a special course. [Hromatograficheskie metody analiza: Metodicheskoe posobie dlya special’nogo kursa]. Moscow: Lomonosov Moscow State University; 2007: 73. (in Russian)

3. GPhM.1.1.0012.15 “Validation of analytical methods” State Pharmacopoeia of the Russian Federation. Moscow, 2018: 14(1). (in Russian)