Analytical and semipreparative resolution of ranolazine enantiomers by liquid chromatography using polysaccharide chiral stationary phases

Abstract

Novel HPLC methods were developed for the analytical and semipreparative resolution of new antianginal drug ranolazine enantiomers. Good baseline enantioseparation was achieved using cellulose tris (3,5-dimethylphenylcarbamate) (CDMPC) chiral stationary phases (CSPs) under both normal-phase and polar organic modes. The validation of the analytical methods including linearity, LODs, recovery, and precision, and the semipreparative resolution of ranolazine racemate were carried out using methanol as mobile phase without any basic and acidic additives under polar organic mode, using CDMPC CSPs. At analytical scale, the elution times of both enantiomers were less than 7.5 min at 20 degrees C and 1.0 mL/min, with the separation factor (a) 1.88 and the resolution factor (R(s)) 2.95. At semipreparative scale, about 14.3 mg/h enantiomers could be isolated and elution times of both enantiomers were less than 13 min at 2.0 mL/min. To increase the throughput, the technique of overlapping injections was used. The first eluted enantiomer was isolated with a purity of 99.6% enantiomer excess (e.e.) and > 99.0% yield. The second enantiomer was isolated with a purity of 98.8% e.e. and > 99.0% yield. In addition, optical rotation and circular dichroism spectroscopy of both ranolazine enantiomers isolated were also investigated.

Sensitive quantification of ranolazine in human plasma by liquid chromatography–tandem mass spectrometry with positive electrospray ionization

“…The fast analysis has a total run time only 2 min per sample. This approach shows much higher throughput than previous reports [6], and is amenable for high-throughput analysis of large sample batches. The method described has been shown to be successfully applied to phase I pharmacokinetic studies in healthy subjects.…”

“…Since ranolazine lacks strong characteristic UV absorption, a HPLC-UV detection method does not provide suitable sensitivity and selectivity for the determination of ranolazine in biological samples [6]. Herron et al [5] developed a LC-MS strategy with solid-phase extraction (SPE) procedure for estimation of ranolazine and its metabolites in human plasma, but it was not sensitive enough for pharmacokinetic studies and did not provide a detailed description of the method.…”

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“…Sharma et al, [11] have developed a new isocratic validated stability indicating liquid chromatographic method using HiQ Sil C-18 HS column and mobile phase methanol: Water (99:1) with detection wave length 273 nm and the linearity was observed as 10-400 µg/mL. Luo et al, [12] have developed an analytical and semipreparative resolution of the enantiomers of Ranolazine using cellulose tris (3, 5 dimethyl phenyl carbamate chiral stationary phases. The retention times of the enantiomers were <7.5 min with flow rate 1.0 ml/min on the analytical scale with resolution greater than 2.…”

Development and Validation of UV Spectroscopic Method for Estimation of Ranolazine in Tablet Dosage Form

“…Few spectrophotometric [8], HPLC [8,9,10], LC-MS [11,17,13] and LCMS-MS [12,18] methods were reported in literature for determination of RAN. However, most of these reported in combination and most of these methods were related to the quantitative assay of RAN in human or dog plasma [7,14,15,16].…”