Determination of Irinotecan enantiomer impurity in Irinotecan Hydrochloride API by using reverse-phase liquid chromatography
Abstract
To evaluate and quantify Irinotecan (R-enantiomer) / Irinotecan related compound D in Irinotecan hydrochloride trihydrate API, a high stereo-specific liquid chromatography technique was developed and validated. The partition was accomplished on ChiralpakIC-3 (150 x 4.6 mm 3µm) through a mobile fragment comprising 0.1 % v/v Formic acid in water and acetonitrile with 1mL/min, 250C, 20µL, 50C and 370 nmas flow rate, column temparture, injection volume, sample cooler temperature and detection wavelength. At 8.903 and 9.75 min, the retention time of Irinotecan (R-enantiomer) and Irinotecan (S-enantiomer) was determined. The resolution between Irinotecan (R-enantiomer) and Irinotecan (S-enantiomer) was found to be 2.4. The impurity acceptance limit is 0.2 %. The established method's precision, accuracy, sensitivity, linearity, specificity, and ruggedness were all verified in accordance with ICH recommendations. The qualifying sample LOQ was found to be 0.4 g/ml, while the minimal amount of sample needed for LOD detection was found to be 0.12 g/ml. The proposed reversed-phase method has been sophisticated and authenticated in accordance with ICH criteria and is capable of quantifying irinotecan enantiomer in irinotecan hydrochloride trihydrate API at trace level concentration. The specificity, linearity, and accuracy of the approach were used to guarantee its efficacy; as a result, it is appropriate for the task at hand, may be used successfully for routine laboratory analysis, and can be utilised for quality control.
Keywords: Irinotecan, liquid chromatography technique, enantiomer impurity
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References
2. https://www.drugs.com/monograph/irinotecan.html
3. Kumar R, Singla RK. Impurities in Pharmaceutical Dosage Form: A Subject Matter of Great Concern. WebmedCentral Pharmaceutical Sciences 2012;3(1):WMC002884. https://doi.org/10.9754/journal.wmc.2012.002884
4. Rebizi, Mohamed &Sеkkoum, Khаlеd&Belboukhari, Nasser &Abdelkrim, Cheriti&Aboul-Enein, Hassan. Chiral separation and determination of enantiomeric purity of the pharmaceutical formulation of cefadroxil using coated and immobilized amylose-derived and cellulose-derived chiral stationary phases. Egyptian Pharmaceutical Journal, 2016; 15: 88-97. https://doi.org/10.4103/1687-4315.190399
5. Aboul-Enein HY, Ali I. Polysaccharide-based chiral stationary phases, Chapter 2 in chiral separation by liquid chromatography and related technologies. New York, NY: Marcel Dekker Inc.; 2003; 21-88. https://doi.org/10.1201/9780203911112.ch2
6. Ravikumar M, Narasimhanaidu M, Srinivasulu K, Raju TS, Reddy MRS, Swamy PY. Enantiomeric separation of docetaxel starting material by chiral LC using amylose-based stationary phase. Chromatographia, 2009; 69:163-167 https://doi.org/10.1365/s10337-008-0837-6
7. Aboul-Enein HY, Ali I. Studies on the effect of alcohols on the chiral discrimination mechanisms of amylose stationary phase on the enantioseparation of nebivolol by HPLC. Journal of Biochemical and Biophysical Methods, 2001; 48(2):175-188. https://doi.org/10.1016/S0165-022X(01)00148-8
8. Ishii K, Minato K, Nishimura N, Miyamoto T, Sato T. Direct chromatographic resolution of four optical isomers of diltiazem hydrochloride on a Chiralcel OF column. Journal of Chromatography, 1994; 686:93-100. https://doi.org/10.1016/S0021-9673(94)89012-9
9. Khan M, Viswanathan B, Rao DS, Reddy R. Chiral separation of frovatriptan isomers by HPLC using amylose based chiral stationary phase. Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences, 2007; 846(1-2):119-123. https://doi.org/10.1016/j.jchromb.2006.08.033
10. Nadalini G, Dondi F, Massi A, Dondoni A, Zhang T, Cavazzini A. Highperformance liquid chromatographic separation of dihydropyrimidineracemates on polysaccharide-derived chiral stationary phases. Journal of ChromatographyA, 2006; 1126(1-2):357-364. https://doi.org/10.1016/j.chroma.2006.05.095
11. Chen L, Zhang LF, Ching CB, Ng SC. Synthesis and chromatographic properties of a novel chiral stationary phase derived from heptakis (6-azido6-deoxy-2,3-di-O-phenylcarbamoylated)-beta-cyclodextrin immobilized onto amino-functionalized silica gel via multiple urea linkages. Journal of Chromatography, 2002; 950(1-2):65-74. https://doi.org/10.1016/S0021-9673(02)00043-2
12. Hoffmann CV, Laemmerhofer M, Lindner W. Novel strong cation-exchange type chiral stationary. Journal of Chromatography, 2007; 1161(1-2):242-251. https://doi.org/10.1016/j.chroma.2007.05.092
13. Wang T, Wenslow RM Jr. Effects of alcohol mobile-phase modifiers on the structure and chiral selectivity of amylose tris(3,5-dimethylphenylcarbamate) chiral stationary phase. Journal of Chromatography, 2003; 1015(1-2):99-110. https://doi.org/10.1016/S0021-9673(03)01262-7
14. Dhakane VD, UBALE MB, A validated chiral LC method for the enantiomeric separation of irinotecan hydrochloride on immobilized cellulose-based stationary phase. International Journal of Pharmaceutical Sciences Review and Research, 2013; 19(2):66-69.
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