Separation and quantitation of valacyclovir enantiomers using stability‐indicating chiral liquid chromatography method with a chiral stationary phase of amylose tris‐(3,5‐dimethylphenylcarbamate)

Abstract

The present research developed and validated a new stability‐indicating technique for the stereo‐selectively enantiomers of the antiviral nucleoside analog Valacyclovir hydrochloride (VAL). The chiral separation was performed using normal‐phase high‐performance liquid chromatography (HPLC) with a chiral stationary phase consisting of amylose tris(3‐chloro‐5‐methylphenylcarbamate) and a mobile phase of “n‐hexane, methanol, ethanol, and diethylamine”, flow rate of 0.60 mL/min, column temperature of 30°C, injection volume of 10‐μL, detection wavelength of 254‐nm, and run time of 25‐min. The enantiomers (S‐enantiomer, L‐isomer, R‐enantiomer, and D‐isomer) of Valacyclovir were separated with a resolution of 4.8 and no interference. The validation parameters verified for the proposed method, linearity in a range of 0.1002–24.3486 μg/mL (0.02–4.86%) with a regression coefficient of 0.999, and the accuracy was determined with excellent recoveries ranging from 94.38%–109.97%. The concentrations established for the detection limit and quantitation limit were 0.01% and 0.02%, respectively. The forced degradation experiments were used to assess the stability‐indicating qualities. D‐Valacyclovir impurity was successfully evaluated in release and stability samples of VAL in drug substance and tablet dosage forms using the proposed normal phase chiral HPLC approach.

Separation and quantification of organic‐related impurities of beta‐adrenergic receptor blocking agent propranolol in pharmaceutical solid dosage forms: Impurity profiling using stability‐indicating HPLC method

“…The stability-indicating method for separating and quantifying organic-related impurities in the propranolol is developed in the present study using the HPLC technique [10][11][12][13][14][15][16]. Because the HPLC technique operates in two distinct ways: reversed-phase HPLC used for the separation of most organic compounds) and normalphase HPLC used for the separation of all chiral compounds including the enantiomers and diastereomers [17][18][19].…”

Separation and simultaneous estimation of enantiomers and Diastereomers of muscarinic receptor antagonist Solifenacin using stability‐indicating Normal‐phase HPLC technique with chiral stationary phase amylose tris‐(3,5‐dimethylphenylcarbamate)

“…Thus, each drug must be tested for potency assays and impurity profiling to figure out its quality and safety using stability‐indicating liquid chromatography (LC) techniques 5–16 . LC techniques are very frequently used to separate target analytes from a complex sample mixture without any interference 17–27 …”

“…In this study, the solifenacin (S, R‐enantiomer) and its chiral impurities or stereoisomer (R,S‐isomer, an enantiomer of solifenacin) and diastereomers (S,S‐isomer and R,R‐isomer) were separated well from each other and measured using normal‐phase high‐performance liquid chromatography (NP‐HPLC) with the chiral stationary phase made of amylose tris (3,5‐dimethylphenylcarbamate) coated on silica gel (Chiralpak, AD‐H). The chiral isomers (stereoisomers) and other organic impurities have different biological effects, and they must be measured in medicines, 17–23 therefore, chromatography methods have been used to quantify impurities and keep them well within permitted limits.…”