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An Experimental Design Approach for Impurity Profiling of Valacyclovir-Related Products by RP-HPLC.

Katakam P, Dey B, Hwisa NT, Assaleh FH, Chandu BR, Singla RK, Mitra A - Sci Pharm (2014)

Bottom Line: Linearity was found in the concentration range of 50-150 μg/mL.The S/N ratios in both cases were within the specification limits.Proper peak shapes and satisfactory resolution with good retention times suggested the suitability of the method for impurity profiling of valacyclovir-related drug substances.

View Article: PubMed Central - PubMed

Affiliation: Faculty of Pharmacy, University of Zawia, Az Zawiyah, Libya.

ABSTRACT
Impurity profiling has become an important phase of pharmaceutical research where both spectroscopic and chromatographic methods find applications. The analytical methodology needs to be very sensitive, specific, and precise which will separate and determine the impurity of interest at the 0.1% level. Current research reports a validated RP-HPLC method to detect and separate valacyclovir-related impurities (Imp-E and Imp-G) using the Box-Behnken design approach of response surface methodology. A gradient mobile phase (buffer: acetonitrile as mobile phase A and acetonitrile: methanol as mobile phase B) was used. Linearity was found in the concentration range of 50-150 μg/mL. The mean recovery of impurities was 99.9% and 103.2%, respectively. The %RSD for the peak areas of Imp-E and Imp-G were 0.9 and 0.1, respectively. No blank interferences at the retention times of the impurities suggest the specificity of the method. The LOD values were 0.0024 μg/mL for Imp-E and 0.04 μg/mL for Imp-G and the LOQ values were obtained as 0.0082 μg/mL and 0.136 μg/mL, respectively, for the impurities. The S/N ratios in both cases were within the specification limits. Proper peak shapes and satisfactory resolution with good retention times suggested the suitability of the method for impurity profiling of valacyclovir-related drug substances.

No MeSH data available.


Related in: MedlinePlus

Robustness contour plots of (A) retention time vs. flow rate and pH, (B) retention time vs. flow rate and temperature, and (C) USP tailing factor vs. flow rate and pH
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Figure 4: Robustness contour plots of (A) retention time vs. flow rate and pH, (B) retention time vs. flow rate and temperature, and (C) USP tailing factor vs. flow rate and pH

Mentions: The design matrix of the Box-Behnken model of the RSM and experimental runs for the robustness of the method are provided in Table 2 and Figure 4. Data on the method’s ruggedness are provided in Table 4 and Figure 5. System suitability data are provided in Table 5 showing that it complies with the specified limits. The HPLC chromatogram recorded under the optimized conditions (Figure 3) showed that the retention times of VCR and impurities E and G were 12.2, 29.4, and 7.2 min, respectively. Finally, it was observed that there were no blank interferences with analytes like VCR or impurities E and G (Figure 5), suggesting the specificity of the developed method. The LOD values of the proposed method were found to be 0.0024 μg/mL for impurity E and 0.04 μg/mL for impurity G. The S/N ratios of impurities E and G were calculated as 4.4 and 4.3, respectively. The LOQ values of impurities E and G by the proposed method were found to be 0.0082 μg/mL and 0.136 μg/mL, with S/N ratios of 10.14 and 10.01, respectively. All parameters of method validation lie within the specified limits as per ICH guidelines [4–10].


An Experimental Design Approach for Impurity Profiling of Valacyclovir-Related Products by RP-HPLC.

Katakam P, Dey B, Hwisa NT, Assaleh FH, Chandu BR, Singla RK, Mitra A - Sci Pharm (2014)

Robustness contour plots of (A) retention time vs. flow rate and pH, (B) retention time vs. flow rate and temperature, and (C) USP tailing factor vs. flow rate and pH
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4318202&req=5

Figure 4: Robustness contour plots of (A) retention time vs. flow rate and pH, (B) retention time vs. flow rate and temperature, and (C) USP tailing factor vs. flow rate and pH
Mentions: The design matrix of the Box-Behnken model of the RSM and experimental runs for the robustness of the method are provided in Table 2 and Figure 4. Data on the method’s ruggedness are provided in Table 4 and Figure 5. System suitability data are provided in Table 5 showing that it complies with the specified limits. The HPLC chromatogram recorded under the optimized conditions (Figure 3) showed that the retention times of VCR and impurities E and G were 12.2, 29.4, and 7.2 min, respectively. Finally, it was observed that there were no blank interferences with analytes like VCR or impurities E and G (Figure 5), suggesting the specificity of the developed method. The LOD values of the proposed method were found to be 0.0024 μg/mL for impurity E and 0.04 μg/mL for impurity G. The S/N ratios of impurities E and G were calculated as 4.4 and 4.3, respectively. The LOQ values of impurities E and G by the proposed method were found to be 0.0082 μg/mL and 0.136 μg/mL, with S/N ratios of 10.14 and 10.01, respectively. All parameters of method validation lie within the specified limits as per ICH guidelines [4–10].

Bottom Line: Linearity was found in the concentration range of 50-150 μg/mL.The S/N ratios in both cases were within the specification limits.Proper peak shapes and satisfactory resolution with good retention times suggested the suitability of the method for impurity profiling of valacyclovir-related drug substances.

View Article: PubMed Central - PubMed

Affiliation: Faculty of Pharmacy, University of Zawia, Az Zawiyah, Libya.

ABSTRACT
Impurity profiling has become an important phase of pharmaceutical research where both spectroscopic and chromatographic methods find applications. The analytical methodology needs to be very sensitive, specific, and precise which will separate and determine the impurity of interest at the 0.1% level. Current research reports a validated RP-HPLC method to detect and separate valacyclovir-related impurities (Imp-E and Imp-G) using the Box-Behnken design approach of response surface methodology. A gradient mobile phase (buffer: acetonitrile as mobile phase A and acetonitrile: methanol as mobile phase B) was used. Linearity was found in the concentration range of 50-150 μg/mL. The mean recovery of impurities was 99.9% and 103.2%, respectively. The %RSD for the peak areas of Imp-E and Imp-G were 0.9 and 0.1, respectively. No blank interferences at the retention times of the impurities suggest the specificity of the method. The LOD values were 0.0024 μg/mL for Imp-E and 0.04 μg/mL for Imp-G and the LOQ values were obtained as 0.0082 μg/mL and 0.136 μg/mL, respectively, for the impurities. The S/N ratios in both cases were within the specification limits. Proper peak shapes and satisfactory resolution with good retention times suggested the suitability of the method for impurity profiling of valacyclovir-related drug substances.

No MeSH data available.


Related in: MedlinePlus