The thesis is devoted to the development of chromatographic and optical methods of analysis for determination of the residual quantities of some drugs after cleaning of pharmaceutical equipment.
For the first time, the theoretical approach for determination of the main metrological characteristic of analytical methods for quality control of the cleaning of equipment, the maximum permissible measurement error, has been developed. The acceptance criteria (maximal uncertainty of the method, linearity of the calibration curve, limit of quantification, precision and reproducibility) of the validation of the analytical method for quality control of the cleaning of equipment and determination of contamination level are proposed.
Optical methods have been developed and validated: spectrophotometric (tilorone,
L-5-hydroxytryptophan, collagen, benzobital), polarimetric (glucose), luminescent (rosuvastatin calcium, flupirtine maleate, abiraterone acetate, rivastigmine hydrotartrate) and atomic emission with inductively coupled plasma (microquantities of potassium and sodium) determination of residual amounts of APIs on surfaces of pharmaceutical equipment in the production of appropriate drugs.
The analytical conditions for the HPLC determination of the APIs are optimized (sorbent type, geometry and column temperature, eluent composition, concentration range of organic modifier in mobile phase, wavelength, etc.). The procedure for the determination of the residual amounts of L-valine,
L-leucine and L-isoleucine in rinse after cleaning of the pharmaceutical equipment by the reversed-phase HPLC method with UV detection was developed and validated using di-tert-butyldicarbonate for pre-column derivatization, which is used in organic synthesis to protect the amino groups. HPTLC was used to determine the residual amounts of dry extract of the leaves of ginkgo biloba (by quercetin content). The method is realized due to the use of phosphoric acid, which prevents the complexation of quercetin with zinc silicate (II) (a component of the fluorescent indicator of the chromatographic plate).
It is shown that the analytical and validation characteristics of the developed methods (linearity range of the method, LOQ, MPC) correspond to the acceptance criteria of the determination of residual amounts of APIs in rinse after after cleaning of the pharmaceutical equipment.
