ВАЛІДАЦІЯ МЕТОДИКИ КІЛЬКІСНОГО ВИЗНАЧЕННЯ КРОМОГЛІКАТУ НАТРІЮ В ОЧНИХ КРАПЛЯХ ПРОТИАЛЕРГІЙНОЇ ДІЇ
DOI:
https://doi.org/10.11603/2312-0967.2015.2.4761Abstract
Validation studies of cromoglicate sodium assay at eye drops with antiallergic action
Е. G. Fetisova
NationalUniversityofPharmacy,Kharkov
Introduction. Today during pharmaceutical development of drugs as well as at the all stage of product lifecycle, significant sense obtain analytical supporting of experiments and estimation of analytical methods which are necessary for control of process and finished products. The analytical methods, conditions of their carrying out, reagents and standard samples should be standardized with aim to obtain reproducing results that are required at the carrying out of drug pharmaceutical development and at the composition of drug registration materials. In accordance with the requirements of the State Pharmacopoeia of Ukraine (SPU) all methods of drug quality control should be validated and proved experimentally that the method is available for intended purposes. We have developed eye drops with antiallergic action based on cromoglicate sodium (CS) and the method of quantitative determination of cromoglicate sodium at the eye drops by the spectrophotometric method. The aim of the work is the determination of the method validation characteristics and experimental evidence that the method can make reliable and reproducing results for the test “Assay”.
Materials and methods. The drug in the form of eye drops based on CS in the therapeutic concentration of 2% was the object of study. CS produced by company "Fermion" (Finland) and conformed to European Pharmacopoeia, was used for preparing of the eye drops. Absorption spectrophotometry in the UV region (SPU, 2.2.25) was the method of study. Analytical equipment: spectrophotometer UV-VIS HP 8453, company "Hewlett Packard" (USA); laboratory digital scales VA-210S, firm "Sartorius" (Germany); measuring vessels accuracy class A.
Results and discussion. Validation of the developed method of quantitative determination of CS have been conducted in accordance with the requirements of SPU by major validation characteristics: specificity, accuracy, precision (convergence), linearity, range, intermediate precision. Also, the calculation of estimated total uncertainty of the analysis have been carrying out. According to the requirements of SPU the concentrations range for the study of linearity, accuracy and convergence has been ranged from 80 % to 120 % in increments of 5 %, the eligibility criteria was designed for B = 5 %, so the maximum uncertainty analysis should not exceed 1.6 %. Method characterized by sufficient convergence and accuracy throughout the range of concentrations studied. Found the relative size of the confidence interval (ΔΖ = 1,23 %) is less than the critical value for the convergence of the results (1,6 %). Systematic error of the method (δ = 0,04 % < 0,41) is almost insignificant. Specificity is confirmed by insignifican deposit "placebo" in the total amount of background absorption compared with the maximum allowable uncertainty analysis (∆As = 1,6 %) and excipients do not interfere with the quantitative determination of CS in the preparation. Intermediate precision of the analysis have been confirmed by the compliance of the relative confidence interval for 6 replicates of a series of eye drops with 2 % CS (ΔΖ = 0,62 %) to acceptance criteria (≤ 1,6 %). Full predicted uncertainty of the test results for the "Assay" of cromoglicate sodium (ΔAs = 1,42 %) is less than critical value (1,6 %), so the method will give correct results in other laboratories on this indicator.
Conclusion. The method of quantitative determination of CS at the eye drops by the spectrophotometric method has been validated in accordance with the requirements of the State Pharmacopoeia of Ukraine. For the test it has been established accordance to specified acceptance criteria for the assay limits ±5% by the validation parameters: specificity, linearity, precision (precision), accuracy within the using range (80-120% of the nominal contents). The complete uncertainty forecast of the method was carried out in order to confirm it correctness when reproduce at other laboratories and it was established that the projected total uncertainty of the results wasn’t exceed the required acceptance criteria. Based on the results of validation studies it has been substantiated and verified experimentally that the test can make reliable results, can be correctly reproduced and be suitable for quality control of 2% eye drops based on CS during differing stage of product lifecycle.
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