[Show abstract][Hide abstract] ABSTRACT: A rapid and sensitive LC–MS–MS method for the simultaneous determination of escin Ia and isoescin Ia in rat plasma, urine, feces and bile samples was developed and validated. Analytes and telmisartan [internal standard (IS)] were extracted by solid-phase extraction on C18 cartridges. Components in the extract were separated on an HC-C18 column (5 μm, 150 × 4.6 mm i.d.) using 10 mM ammonium acetate–methanol–acetonitrile (40:30:30, v/v/v) as the mobile phase. The method demonstrated good linearity from 5 ng mL−1 (LLOQ) to 1,500 ng mL−1 for both escin Ia and isoescin Ia. Intra- and inter-day precision measured as RSD was within ±15%. Recoveries and matrix effects of both escin Ia and isoescin Ia were satisfactory in all four matrices examined. The method was successfully applied to a pharmacokinetic study in Wistar rats after a single intravenous administration of escin Ia at the dose of 1.0 mg kg−1
[Show abstract][Hide abstract] ABSTRACT: A rapid and sensitive LC-MS-MS method for the quantitation of sertraline in human plasma was developed and validated. Sertraline and the internal standard, telmisartan, were cleaned up by protein precipitation from 100 μL of plasma sample, and analyzed on a TC-C18 column (5 μm, 150 × 4.6 mm i.d.) using 70% acetonitrile and 30% 10 mM ammonium acetate (0.1% formic acid) as mobile phase. The method was demonstrated to be linear from 0.1 ng/mL to 50 ng/mL with the lower limit of quantitation of 0.1 ng/mL. Intra- and inter-day precision were below 4.40% and 3.55%. Recoveries of sertraline at low, medium, and high levels were 88.0 ± 2.3%, 88.2 ± 1.9%, and 90.0 ± 2.0%, respectively. The method was successfully applied to a bioequivalence study of sertraline after a single oral administration of 50 mg sertraline hydrochloride tablets.
Journal of chromatographic science 02/2011; 49(2):89-93. · 1.03 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A highly sensitive liquid chromatography-tandem mass spectrometry (LC-MS-MS) method for the determination of troxerutin in human plasma using tramadol as internal standard (IS) has been developed and validated. Sample preparation involved liquid-liquid extraction with ethyl acetate-isopropanol (95:5, v/v). The analyte and IS were separated by RP-LC with gradient elution using 10 mM ammonium acetate containing 0.1% formic acid and methanol at a flow rate of 0.9 mL min(-1). LC-MS-MS in the positive ion mode employed multiple reaction monitoring of the transitions at m/z 743.2 -> 435.3 and m/z 264.1 -> 58.0 for troxerutin and IS, respectively. The assay was linear in the concentration range 0.01-10 ng mL(-1) with precision and accuracy within assay variability limits as per FDA guidelines. The assay was successfully applied to a pharmacokinetic study involving oral administration of 300 mg troxerutin to eight healthy Chinese volunteers.
[Show abstract][Hide abstract] ABSTRACT: Felbinac trometamol (trishydroxymethylaminomethane 4-biphenylacetate) is a new water-soluble salt of felbinac currently undergoing clinical evaluation as an intravenous (i.v.) formulation for the treatment of severe post-operative pain. This article reports the pharmacokinetics of felbinac after i.v. administration of felbinac trometamol in Sprague-Dawley rats. The maximum plasma concentration (C(0)) and area under the plasma concentration-time curve (AUC) of felbinac administered at doses of 3.36, 8.40 and 21.0 mg/kg felbinac trometamol increased linearly with dose. Felbinac was highly protein bound (~95%) at plasma concentrations up to 75 μg/ml and extensively metabolized with only small amounts being excreted unchanged in urine (0.318%), feces (0.530%) and bile (0.465%). 4'-Hydroxyfelbinac was the principal metabolite in urine, feces and bile together with felbinac glucuronide, 4'-hydroxyfelbinac glucuronide and sulfate. The majority of the administered dose was excreted in urine (63.6%) mostly as 4'-hydroxyfelbinac. Total drug in urine and feces accounted for about 72% of the dose. It would appear that felbinac trometamol has the potential to replace lipid-based NSAID formulations and progress to clinical evaluation.
[Show abstract][Hide abstract] ABSTRACT: A rapid and sensitive method for the simultaneous quantitation of hydrochlorothiazide (HCT) and metoprolol (MET) in human plasma based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been developed and validated. MS/MS detection involved switching the electrospray ionization (ESI) mode during chromatography from negative to detect HCT and its internal standard (I.S.) 5-bromouracil to positive to detect MET and its I.S. tramadol. Sample preparation by liquid-liquid extraction with diethyl ether-dichloromethane (60:40, v/v) was followed by chromatography on a Venusil MP-C18 column using methanol-ammonium acetate (10mM)-formic acid (pH 3.4) (50:50:0.05, v/v/v) at a flow rate of 0.8mL/min. The method was linear in the concentration range 3-1000ng/mL for both HCT and MET using 100microL human plasma. Intra- and inter-day precisions (as relative standard deviation) for HCT were 2.9-3.9% and 3.9-4.7%, respectively and for MET were 2.4-4.1% and 4.7-6.2%, respectively. Accuracies (as relative error) were +/-3.8% and +/-2.6% for HCT and MET, respectively. The assay was successfully applied to a pharmacokinetic study involving a single oral dose of a combination tablet (25mg HCT, 50mg MET) in healthy volunteers.
Journal of pharmaceutical and biomedical analysis 05/2010; 52(1):149-54. · 2.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A rapid and sensitive method based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been developed for the determination of octahydroaminoacridine in human plasma using tramadol as internal standard (I.S.). Sample preparation involved pH adjustment with sodium carbonate followed by solvent extraction with dichloromethane:ethyl ether (40:60, v/v). Chromatographic separation was achieved on a Venusil MP-C18 column (5 microm, 100 mm x 4.6mm) using acetonitrile:10mM ammonium acetate:formic acid (30:70:1, v/v/v) as mobile phase. Detection utilized an API 4000 system operated in the positive ion mode with multiple reaction monitoring of the analyte at m/z 203.1-->175.1 and of the I.S. at m/z 264.1-->58.0. The method was linear in the range 0.01-10 ng/ml with a lower limit of quantitation of 0.0 1ng/ml. Intra- and inter-day precisions measured as relative standard deviation were <3.15% and <5.01%, respectively. The method was successfully applied to a pharmacokinetic study involving oral administration of a tablet containing 4 mg octahydroaminoacridine succinate to healthy volunteers. Pharmacokinetic parameters for octahydroaminoacridine include C(max) 1.19+/-0.53 ng/ml, T(max) 0.77+/-0.17 h, AUC(0-t) 3.42+/-1.01 ng h/ml and t(1/2) 2.89+/-0.56 h.
Journal of pharmaceutical and biomedical analysis 04/2009; 50(2):171-4. · 2.45 Impact Factor