Estimation of ranolazine and eleven Phase I metabolites in human plasma by liquid chromatography-atmospheric pressure chemical ionisation mass spectrometry with selected-ion monitoring

Development and validation of a sensitive U-HPLC–MS/MS method with electrospray ionization for quantitation of ranolazine in human plasma: Application to a clinical pharmacokinetic study

“…The stability of quality control plasma samples (5,200 and 2400 ng mL −1 ) were found stable in plasma when placed in the short term (8 h) room temperature, four freeze/thaw (−25 • C) cycles and stored at −75 • C for 2 months. In addition, the stability of ranolazine in processed quality control samples was also found Table 1 Extraction recovery, intra-and inter-day coefficients of variance of ranolazine in human plasma.…”

“…Three different concentration levels of ranolazine (5,200 and 2400 ng mL −1 ) were evaluated by analyzing five samples at each level. Percent nominal concentrations estimated were within the acceptable limits (85.0-100.4%) after evaluating six different lots of plasma.…”

“…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 [4,5]. Recently, two LC-MS methods with selected ion monitoring (SIM) have been published [6,7]; both of them allowed the quantitation of ranolazine in rat plasma with the lower limit of quantitation (LLOQ) above 20 ng mL −1 and relatively long HPLC/MS analysis time (6 or 7 min per sample) [8].…”

Development and validation of a sensitive LC–MS/MS assay for simultaneous quantitation of ranolazine and its three metabolites in human plasma

“…However, very few analytical methods for simultaneously quantitating ranolazine and its metabolites in human plasma have been published in the literature to date. Penman et al developed an LC-MS assay to identify the metabolites of ranolazine in human plasma [10], and Herron et al described another LC/MS method to determine ranolazine and semi-quantitate the observed metabolites [11]. Unfortunately, these two articles did not provide detailed descriptions of the methods used.…”

Synthesis of Ranolazine Metabolites and Their Anti-myocardial Ischemia Activities

“…Figure 2 shows the seven principal metabolic routes of Ranolazine. 18,19) Route one: hydroxylation of the methyl group in the 2,6-dimethylphenyl fragment to produce CVT-2551; route two: hydroxylation of the 2-methoxyphenyl or 2,6-dimethylphenyl group to produce CVT-5029/CVT-5030/CVT-5031 and CVT-5028/CVT-3388 respectively; route three and four: N-dealkylation of the piperazine ring to give the components CVT-2513, CVT-2535, CVT-2738, CVT-2534; route five: O-dearylation to produce CVT-2512; route six: O-demethylation to produce CVT-2514; route seven: hydrolysis of the amide group to produce CVT-3369. Among those metabolites, there are four metabolites should be paid more attention since their blood concentrations exceed 10% of the parent compound concentration.…”