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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

Chemical structures of (A) valacyclovir, (B) impurity E, and (C) impurity G
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Figure 1: Chemical structures of (A) valacyclovir, (B) impurity E, and (C) impurity G

Mentions: Valacyclovir (VCR) is a hydrochloride salt of the L-valyl ester of acyclovir. Chemically, it is 2-[(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)methoxy]ethyl L-valinate (Figure 1A), used for the treatment of herpes simplex and herpes zoster. It is phosphorylated by viral thymidine kinase to acyclovir triphosphate (the active metabolite) which then inhibits herpes viral DNA replication by competitive inhibition of viral DNA polymerase, and by incorporation into and termination of the growing viral DNA chain [8–11].


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)

Chemical structures of (A) valacyclovir, (B) impurity E, and (C) impurity G
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: Chemical structures of (A) valacyclovir, (B) impurity E, and (C) impurity G
Mentions: Valacyclovir (VCR) is a hydrochloride salt of the L-valyl ester of acyclovir. Chemically, it is 2-[(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)methoxy]ethyl L-valinate (Figure 1A), used for the treatment of herpes simplex and herpes zoster. It is phosphorylated by viral thymidine kinase to acyclovir triphosphate (the active metabolite) which then inhibits herpes viral DNA replication by competitive inhibition of viral DNA polymerase, and by incorporation into and termination of the growing viral DNA chain [8–11].

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