Résumé
Objective:To establish a Crownpak CR( +)-HPLC method for the determination of the content and related substance of valacyclovir hydrochloride dispersible tablets. Methods: A Crownpak CR( +) [4. 0 mm × 150 mm,5 μm,DAICEL CROWNPAK CR( +)] column was used,and the mobile phase was 0. 1% perchloric acid in water. The flow rate was 0. 75 ml·min-1 and the de-tection wavelength was 255 nm. Results: A good linear range of valacyclovir hydrochloride was 11. 25-180. 00 μg · ml-1 ( r =1. 000 0), and the average recovery was 99. 0%(RSD=0. 8%, n=9). A good linear range of alacyclovir was 0. 2-50μg·ml-1(r=1. 000 0), and the average recovery was 99. 3%(RSD=0. 6%, n=9). The content of the tablets from two pharmaceutical companies was 92. 7% and 97. 4%, respectively, that of acyclovir calculated by an external standard method was 0. 5% and 0. 4%, respectively, and that of D-valacyclovir calculated by a self-control method was 0. 9%. Conclusion:The method can effectively separate valacyclovir and D-valacyclovir, which is simple, accurate and reliable, and suitable for the quantity control of valacyclovir hydrochloride.
Résumé
Objective:To develop an HPLC method for the determination of valacyclovir hydrochloride capsules. Methods: An Inertsil ODS (250 mm × 4. 6 mm,5μm) column was employed with methanol-0. 02 mol·L-1 potassium dihydrogen phosphate solution (20∶80) as the mobile phase, the flow rate was 1. 0 ml·min-1, the detection wavelength was at 251 nm, the column temperature was 30℃,and the sample size was 20μl. Results:The linear range of valacyclovir hydrochloride was 2-40μg·ml-1 , the correlation coeffi-cient was 0. 999 9 and the average recovery was 99. 8%(RSD=0. 16%,n=9). Conclusion:The analytical method is simple, accu-rate and special, which can be used in the content determination and quality control of valacyclovir hydrochloride capsules.
Résumé
Objective: To establish a rapid, sensitive and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of acyclovir (the metabolite of valacyclovir hydrochloride) in human plasma. Methods: After addition of ganciclovir as internal standard (IS), plasma samples were prepared by one-step protein precipitation using acetonitrile as precipitant, followed by an isocratic elution with 0.1% formic acid solution-methanol (95:5, v/v) on an Agilent ZORBAX SB-C18 (150 mmx2.1 mm i. d., 3.5 μm) column. Detection was performed on a triple-quadrupole mass spectrometer utilizing electrospray ionization (ESI) interface operating in positive ion and selected reaction monitoring (SRM) mode with the precursor to product ion transitions m/z 226.2→152.1 for acyclovir and m/z 256.2→152.1 for the IS. Results: The analytical results demonstrated a good linearity over the ranges from 0.005 to 4 μg/mL (r=0.9999) for valacyclovir hydrochloride. The relative standard deviations (RSD) of intra-batch and inter-batch were less than 4.06% and 9.23%, respectively. The limit of detection and lower limit of quantification in human plasma were 2 ng/mL and 5 ng/mL, respectively. Conclusion: The method was simple, sensitive, accurate and reproducible and has been successfully applied to a bioequivalence study of valacyclovir hydrochloride capsules in Chinese healthy male volunteers.
Résumé
Objective To establish a rapid, sensitive and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of acyclovir (the metabolite of valacyclovir hydrochloride) in human plasma. Methods After addition of ganciclovir as internal standard (IS), plasma samples were prepared by one-step protein precipitation using acetonitrile as precipitant, followed by an isocratic elution with 0.1% formic acid 3.5μm) column. Detection was performed on a triple-quadrupole mass spectrometer utilizing electrospray ionization (ESI) interface operating in positive ion and selected reaction monitoring (SRM) mode with the precursor to product ion transitions m/z 226.2→152.1 for acyclovir and m/z 256.2→152.1 for the IS. Results The analytical results demonstrated a good linearity over the ranges from 0.005 to 4μg/mL (r=0.9999) for valacyclovir hydrochloride. The relative standard deviations (RSD) of intra-batch and inter-batch were less than 4.06% and 9.23%, respectively. The limit of detection and lower limit of quantification in human plasma were 2ng/mL and 5ng/mL, respectively. Conclusion The method was simple, sensitive, accurate and reproducible and has been successfully applied to a bioequivalence study of valacyclovir hydrochloride capsules in Chinese healthy male volunteers.