Abstract
A capillary gas chromatography method with a short run time, using a flame ionization detector, has been developed for the quantitative determination of trace level analysis of mesityl oxide and diacetone alcohol in the atazanavir sulfate drug substance. The chromatographic method was achieved on a fused silica capillary column coated with 5% diphenyl and 95% dimethyl polysiloxane stationary phase (Rtx-5, 30 m x 0.53 mm x 5.0 µm). The run time was 20 min employing programmed temperature with a split mode (1:5) and was validated for specificity, sensitivity, precision, linearity, and accuracy. The detection and quantitation limits obtained for mesityl oxide and diacetone alcohol were 5 µg/g and 10 µg/g, respectively, for both of the analytes. The method was found to be linear in the range between 10 µg/g and 150 µg/g with a correlation coefficient greater than 0.999, and the average recoveries obtained in atazanavir sulfate were between 102.0% and 103.7%, respectively, for mesityl oxide and diacetone alcohol. The developed method was found to be robust and rugged. The detailed experimental results are discussed in this research paper.
Highlights
Atazanavir sulfate is chemically known as (3S,8S,9S,12S)-3,12-bis(1,1-dimethylethyl)8-hydroxy-4,11-dioxo-9-(phenylmethyl)-6-[[4-(2-pyridinyl)phenyl]methyl]-2,5,6,10,13-pentaazatetradecanedioic acid 1,14-dimethyl ester sulfate (1:1)
Each 100 μg/g Mesityl oxide (MO)/ diacetone alcohol (DO) solution was prepared in N,N-dimethylformamide and the same solution was transferred into the headspace vial and sealed with the help of a screw cap
MO was eluted close to N,N-dimethylformamide and DO was eluted after N,N-dimethylformamide with a very low response which may be due to its low volatile nature
Summary
Atazanavir sulfate is chemically known as (3S,8S,9S,12S)-3,12-bis(1,1-dimethylethyl)8-hydroxy-4,11-dioxo-9-(phenylmethyl)-6-[[4-(2-pyridinyl)phenyl]methyl]-2,5,6,10,13-pentaazatetradecanedioic acid 1,14-dimethyl ester sulfate (1:1). Mesityl oxide (MO) is an α,β-unsaturated ketone with the formula CH3C(O)CH=C(CH3) and diacetone alcohol (DO) is a chemical compound with the formula CH3C(O)CH2C(OH)(CH3)2 These two residual impurities are present in commercial grade acetone at trace levels. This research paper describes a simple and sensitive gas chromatography method with a flame ionization detector (FID) for the quantification of MO and DO in the ATV drug substance with limit of detection and limit of quantitation values 0.04 and 0.70 μg/ml, respectively. Transfer 3 ml of internal standard solution into a 10 ml centrifuge tube and add 3 ml of 75% formic acid solution and shake vigorously for 1 min. Weigh and transfer 51 mg each of mesityl oxide and diacetone alcohol into a 50-ml volumetric flask containing about 20 ml of internal standard solution, dilute to volume with the internal standard solution. Shake vigorously for 1 min. until the phases separate and the lower layer (methylene chloride layer) can be collected through a disposable pipette and transferred to a 2-ml vial for GC analysis
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