K.Yu. Kravets – Post-graduate Student, Vernadsky Institute of Geochemistry  and Analytical Chemistry of RAS (Moscow)

E-mail: Konstantin@kravets.ru

Ya.O. Simanovsky – Ph.D. (Phys.-Math.), Senior Research Scientist, 

Prokhorov General Physics Institute of RAS (Moscow)

E-mail: yasimanovskiy@mail.ru

A.A. Grechnikov – Dr.Sc. (Chem.), Leading Research Scientist, Vernadsky Institute of Geochemistry  and Analytical Chemistry of RAS (Moscow)

E-mail: agrech@bk.ru

Statement of the problem. Method for mass spectrometric analysis of medicines without preliminary sample preparation based on Atmospheric Pressure Laser Plasma Ionization (APLPI) technique has been developed. Laser plasma is a source of hard ultraviolet radiation and is used to create a high concentration of primary ions, which provide subsequent soft ionization of analyte molecules as a result of ion-molecular interactions. 

Aim of the work – the results of the study of the APLPI method in combination with a high-resolution mass analyzer for solving the problem of rapid analysis of drugs are presented.

Results. Developed ion source is based on a combination of a pulsed Nd:YAG laser creating the laser plasma and thermal desorption sample inlet. The laser radiation is focused on the surface of a metal target placed near the inlet of the «Orbitrap» mass analyzer. 13 marketed drugs were investigated. The samples were introduced into the ionization zone in two ways: by using an evaporating metal microcuvette or by exposing the solid dosage form to a stream of hot air. The drugs were analyzed without preliminary sample preparation.

For all studied drugs, the mass spectra were recorded. All obtained mass spectra uniquely characterize the active drug substances. The mass spectra are simple and easy to interpret. It was established that, depending on the chemical properties of the analytes, three different channels of ionization are realized. The first channel is ionization by protonation, and it was observed for all the compounds studied. This channel is the main one for compounds with high values of proton affinity energies. The second channel is based on reactions of electrophilic addition with the formation of adducts with ammonium. It is the main one for the studied oxygen-containing compounds with moderate values of proton affinity energies. The third ionization channel leads to the formation of molecular ions.

In the mass spectra of a number of drugs, peaks of ions of auxiliary substances or excipients with low molecular weight are detected. On the example of determining melatonin, it was shown that the detection of such components can be used to distinguish drugs with the same active substance from different manufacturers. The method was also tested for the analysis of complex multicomponent medicines without sample preparation.

It was shown that the duration of the analysis with the sample injection by the evaporating microcuvette is 2–3 minutes, and it takes several seconds when the drug is exposed to a stream of hot air.

Practical significance. The developed method can be used at different stages of the development of new drugs, for studying the degradation of active substances in tablets or capsules, for the rapid detection of counterfeit products.

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