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A sensitive LC–MS/MS method was developed and fully validated for the determination of spironolactone in human plasma using spironolactone-d6as an internal standard (IS) after one-step liquid–liquid extraction with methyl tert-butyl ether: methylene chloride (MC) = 8:2 (v/v). Detection was performed using electrospray ionization in positive ion multiple reaction monitoring mode by monitoring the transitions: m/z341.2 → 107.2 for spironolactone and m/z347.1 → 107.2 for IS. Chromatographic separation was performed on a Cadenza CD-C18column (3.0 × 100 mm i.d. 3 µm) with an isocratic mobile phase, which consisted of 0.1 % formic acid in water: methanol (30: 70, v/v), with a gradient flow rate as follow: 0–3.2 m, 320 µL/min; 3.2–3.5 m, 320–180 µL/min; 3.5–6.7 m, 180 µL/min; 6.7–7.0 m, 180–320 µL/min. The calibration curve was linear (correlation coefficients were >0.99) over the concentration range (0.5–150 ng/mL). The intraday and interday precisions ranged 0.89–6.00 and 1.20–10.511 %, respectively, and its accuracies ranged 96.90–105.08 and 97.99–104.13 %, respectively. The devised method was successfully applied in a bioequivalence study of two formulations of spironolactone, Spiracton tablet®and Aldactone tablet®in 50 healthy Korean male volunteers following single oral administration.

A sensitive and specific liquid chromatographic method coupled with tandem mass spectrometry was developed and validated for the analysis of ketotifen. After treated by liquid–liquid extraction, ketotifen and the oxybutinin (internal standard, IS) were eluted on a Luna C18 column. The isocratic mobile phase was consisted of 10 mM ammonium formate (pH = 3) and acetonitrile (5:95, v/v), with flow rate at 0.2 mL/min. A tandem mass spectrometer, as detector, was used for quantitative analysis in positive mode by a multiple reaction monitoring mode to monitor the m/z310.2 → 96.2 and the m/z358.2 → 142.2 transitions for ketotifen and the IS, respectively. Forty-six healthy Korean male subjects received two tablets (1 mg × 2) of either the test or the reference formulation of ketotifen in a 2 × 2 crossover study, this was followed by a 1 week washout period between either formulation. AUC0−t(the area under the plasma concentration–time curve) was calculated by the linear trapezoidal rule. Cmax(maximum plasma drug concentration) and Tmax(time to reach Cmax) were compiled from the plasma concentration–time data. The 90 % confidence intervals for the log transformed data were acceptable range of log 0.8 to log 1.25 (e.g., log 0.9241 − log 1.0636 for AUC0−tlog 0.9165 − log 1.0550 for Cmax). The major parameters, AUC0−tand Cmaxmet the criteria of Korea Food and Drug Administration for bioequivalence indicating that Fumatifen®tablet (test) is bioequivalent to Zaditen®tablet (reference).A sensitive and specific liquid chromatographic method coupled with tandem mass spectrometry was developed and validated for the analysis of ketotifen. After treated by liquid–liquid extraction, ketotifen and the oxybutinin (internal standard, IS) were eluted on a Luna C18 column. The isocratic mobile phase was consisted of 10 mM ammonium formate (pH = 3) and acetonitrile (5:95, v/v), with flow rate at 0.2 mL/min. A tandem mass spectrometer, as detector, was used for quantitative analysis in positive mode by a multiple reaction monitoring mode to monitor the m/z310.2 → 96.2 and the m/z358.2 → 142.2 transitions for ketotifen and the IS, respectively. Forty-six healthy Korean male subjects received two tablets (1 mg × 2) of either the test or the reference formulation of ketotifen in a 2 × 2 crossover study, this was followed by a 1 week washout period between either formulation. AUC0−t(the area under the plasma concentration–time curve) was calculated by the linear trapezoidal rule. Cmax(maximum plasma drug concentration) and Tmax(time to reach Cmax) were compiled from the plasma concentration–time data. The 90 % confidence intervals for the log transformed data were acceptable range of log 0.8 to log 1.25 (e.g., log 0.9241 − log 1.0636 for AUC0−tlog 0.9165 − log 1.0550 for Cmax). The major parameters, AUC0−tand Cmaxmet the criteria of Korea Food and Drug Administration for bioequivalence indicating that Fumatifen®tablet (test) is bioequivalent to Zaditen®tablet (reference).