Application of the gas chromatography-mass spectrometry method for the identification of standard samples of ACE inhibitors drugs

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Abstract

Introduction. To date, quality control and standardization of drugs, including medicines from the group of angiotensin-converting enzyme inhibitors (ACE inhibitors), as a rule, involves the use of reference standards (RS). In the process of RS development, a number of comprehensive tests are carried out in compliance with the requirements governing the quality of standards. One of the key values of RS quality is the definition of authenticity. Objective: to study the possibility of using the chromatography-mass spectrometric method to determine the identity of RS of antihypertensive medicines of the ACE inhibitor group. Material and methods. As part of the development of RS, the investigated samples of Captopril and Enalapril maleate substances were used. Chromatography-mass spectra of solutions of the studied samples were recorded on a Zhimadzu Nexera liquid chromatograph with a Shimadzu LCMS-8050 mass-selective detector using the following types of ionization - APCI and HESI. Results. The reliability, high sensitivity, accuracy, the informational content of the mass spectrometric method is shown on the example of the identification of the developed RS of Captopril and Enalapril maleate. The determination of the molecular ion and the study of the fragmentation scheme of the main molecular ions in the mass spectra allows us to successfully identify the studied samples of Captopril and Enalapril maleate. Conclusion. Experimental data obtained during the study of samples of Captopril and Enalapril maleate can be used both in quality control of the corresponding RS and in the pharmaceutical analysis of medicinal products containing the same pharmaceutical substances.

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About the authors

Dmitry Andreevich Chepilo

Sechenov First Moscow State Medical University (Sechenov University)

Author for correspondence.
Email: z22dima@mail.ru
Ph.D. student of the Department of pharmaceutical and toxicological chemistry named after A.P. Arzamastsev, Institute of pharmacy named after A.P. Nelyubin

Vladimir Iraklievich Gegechkori

Sechenov First Moscow State Medical University (Sechenov University); Peoples' Friendship University of Russia

Email: vgegechkori@gmail.com
Ph.D. in pharmaceutical sciences, associate professor of the Department of pharmaceutical and toxicological chemistry named after A.P. Arzamastsev, Institute of pharmacy named after A.P. Nelyubin; senior teacher of the department of microbiology and virology, faculty of medicine

Olga Yuryevna Shchepochkina

Sechenov First Moscow State Medical University (Sechenov University)

Email: shchepochkina_o_yu@staff.sechenov.ru
Ph.D. in pharmaceutical sciences, associate professor of the Department of pharmaceutical and toxicological chemistry named after A.P. Arzamastsev, Institute of pharmacy named after A.P. Nelyubin

Natalia Nikolaevna Chadova

State Institute of Drugs and Good Practices and Good Practices

Email: chadovann@gilsinp.ru
Ph.D. of chemical sciences, head of the department for inspection of production of medicines and expertise

Anatolii Anatolevich Levko

State Institute of Drugs and Good Practices and Good Practices

Email: levko.aa@gilsinp.ru
Ph.D. of medical sciences, deputy head of the department for inspection of production of medicines and expertise

Vladislav Nikolaevich Shestakov

State Institute of Drugs and Good Practices and Good Practices

Email: shestakov@gilsinp.ru
director

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Supplementary files

Supplementary Files
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2. Fig. 1. Structural formulas of (а) Captopril and (b) Enalapril (Enalapril maleate)

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3. Fig. 2. Mass spectrum of the investigated sample of Captopril (APCI+, HPLC-MS)

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4. Fig. 3. Molecular ion fragmentation [M+H]+=218 м/з of the investigated sample Captopril (APCI+, HPLC-MS)

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5. Fig. 4. Probable scheme of fragmentation of the main molecular ion [M+H]+=218 м/з of the investigated sample of Captopril (APCI+, HPLC-MS)

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6. Fig. 5. Mass spectrum of the investigated sample of Captopril (APCI-, HPLC-MS)

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7. Fig. 6. Molecular ion fragmentation [M-H]–=216 м/з of the investigated sample Captopril (APCI–, HPLC-MS)

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8. Fig. 7. Probable scheme of fragmentation of the main molecular ion [M-H]–=216 м/з of the investigated sample of Captopril (APCI–, HPLC-MS)

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9. Fig. 8. Mass spectrum of the investigated sample of Enalapril maleate (HESI+, HPLC-MS)

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10. Fig. 9. Molecular ion fragmentation [M+H]+=377 м/з of the investigated sample Enalapril maleate (HESI+, HPLC-MS)

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11. Fig. 10. Probable scheme of fragmentation of the main molecular ion [M+H]+=377 м/з of the investigated sample of Enalapril maleate (HESI+, HPLC-MS)

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12. Fig. 11. Mass spectrum of the investigated sample of Enalapril maleate (HESI–, HPLC-MS)

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13. Fig. 12. Molecular ion fragmentation [M-H]–=375 м/з of the investigated sample Enalapril maleate (HESI–, HPLC-MS)

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14. Fig. 13. Probable scheme of fragmentation of the main molecular ion [M-H]–=375 м/з of the investigated sample of Enalapril maleate (HESI–, HPLC-MS)

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