VALIDATION OF METHODS FOR DETERMINING RESIDUAL AMOUNTS OF RIBOXIN ON THE SURFACE OF EQUIPMENT
DOI:
https://doi.org/10.11603/2312-0967.2016.2.6647Keywords:
validation of cleaning, residual amounts, UV-spectrophotometry, riboxine.Abstract
Introduction. In the industrial manufacture of active pharmaceutical ingredients and drugs based on them to prevent contamination of one product by the previously manufactured one an important step of production is cleaning of the equipment. It includes a number of procedures, among them there is sampling (the method of swabs or smears) and validated tests for residual amounts of active pharmaceutical ingredients (APIs) on the surfaces of equipment [1-4].
Typically, the acceptance limits for residual amounts of APIs on the surfaces of equipment is calculated on basis of the criteria of risk associated with the residues of these ingredients [5, 6]. According to the PIC/S (Pharmaceutical inspection cooperation scheme) recommendations the permissible residual amount of the drug must meet the following criteria:
- there should be no visible traces on the equipment upon completion of cleaning;
- not more than 0.1% of the mean therapeutic dose of any previously manufactured product can be in the maximum daily dose of the drug;
- a drug should not contain more than 10 ppm of any other drug.
To determine residual amounts of APIs the methods with a high selectivity in relation to the analyte and impurities – degradation products appearing in the process of washing and with a high sensitivity are used. Usually these methods are high-performance liquid chromatography (HPLC) [1-5] fluorimetry [7, 11] and UV spectroscopy [13, 14].
The aim of this work was to develop and validate a simple and selective method for determining residual amounts of riboxin in smears from surfaces of the equipment cleaned after production of riboxin tablets.
Investigation methods. The analytical studies were performed by spectrophotometry using a Specord 205 spectrophotometer by “Analytik Jena AG” company (Germany), OHAUS AP 250D electronic laboratory scales by “Ohaus Corporation” firm (USA) and glassware for measuring of class A.
Smears from the equipment surface were collected using cotton swabs moistened with water. Determination of residual amounts of riboxin was performed by measuring optical density of the test solution and the reference solution with the subsequent comparison of the results. As a standard sample 9-β-D-ribofuranosyl hypoxanthine (riboxin (inosine), batch 1 dated 20.04.2012 (RS, SPhU) was used.
Results and discussion. Recently, much attention is given to cleaning of the manufacturing equipment from the residue of APIs when producing drugs. According to the guidelines “Drugs. Good Manufacturing Practice 2015. 42-4.0: 2015” [12] the process of the manufacturing equipment cleaning must provide such purity that is necessary for production of drugs. To meet these conditions there should be sensitive, specific, validated methods controlling residual amounts of APIs of the manufacturing equipment.
According to the requirements of the Chinese Pharmacopoeia [8,9] and RF Pharmacopoeia [10] the quantitative determination of the riboxin substance is determined by liquid chromatography, which is long-term and cannot comply with the technological process. The analytical method used should be selective, sensitive and express. Therefore, the attempt to develop such a method has been made.
The spectral studies conducted show that the UV absorption spectrum of 10 ppm of riboxin aqueous solution in the range from 220 nm to 300 nm is characterized by the absorption maximum at a wavelength of (249 ± 2) nm. The absence of the placebo effect (swabs from a pure plate of the equipment) on determination of riboxin has been confirmed.
The criterion of bias insignificance of the method has been performed; the systematic error of the method (0.02) is statistically and practically insignificant, i.e. the method of analysis is characterized by sufficient accuracy within the whole range of concentrations from 0.5 to 10.0 ppm.
The parameters of “Yi = b • Xi + a” linear dependence were calculated by the least square method. The results indicate compliance with the parameters of the linear dependence; linearity of the method has been confirmed within the whole range of concentrations from 0.5 to 10.0 ppm.
The predicted total uncertainty of the results (1.55%) does not exceed the critical value (1.60%), i.e. the method will give correct results in other laboratories.
Conclusions. The spectrophotometric method for determining residual amounts of riboxin has been developed. It can be used for quality control of cleaning the manufacturing equipment.References
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