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A validated chiral LC method for the enantiomeric separation of abacavir key intermediate, ABC-3

P.Radhakrishnanand, D.V.Subba Rao, V.Himabindu

A new and accurate chiral liquid chromatographic method was described for the enantiomeric separation ofABC-3 [N-(2-amino-4-chloro-6-{[(4R)- 4-(hydroxymethyl) cyclopent-2-en-1-yl]amino}pyrimidin-5-yl)formamide, (R)-isomer], a key intermediate ofAbacavir in bulk drugs with an elution time of about 15 min. The separation was achieved on immobilized amylose based chiral stationary phase (Chiralpak-IA) using n-hexane: ethanol: 1,4-dioxane (80:15:5, v/v/v) as mobile phase. The mobile phase was delivered at 1.0 mLmin-1 flowand the detection wasmonitored at 230 nm using ultraviolet detection technique. The resolution (Rs) among the enantiomers was found to be 2.9. Themethod shows 0.035g as limit of detection (LOD) and 0.1µg as limit of quantification (LOQ) for [N-(2-amino-4- chloro-6-{[(4S)-4-(hydroxymethyl)cyclopent-2-en-1-yl]amino}pyrimidin-5- yl)formamide, (S)-isomer], for 10Linjection volume.The validatedmethod yielded good results regarding precision, linearity and accuracy. The developedmethod shows excellent linearity (R2>0.999) over a range of LOQ to 0.3%for (S)-isomer. The percentage recovery of (S)-isomer ranged from 96.3-103.1 in bulk drug samples ofABC-3. Robustness studies were also carried out on the developedmethod.ABC-3 sample solution stability and mobile phase stability studies were carried out and the results found to be stable for a study period of 48 h. The proposed method was found to be suitable and accurate for the quantitative determination of (S)-isomer in bulk drug samples ofABC-3.