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As a tool to be used in transporter-mediated drug-drug interaction studies, a sensitive LC-MS/MS method for the simultaneous quantification of adefovir and pitavastatin in human plasma and adefovir in urine was developed and successfully validated. Plasma samples were processed by protein precipitation using methanol with a subsequent concentrating step. Urine samples were diluted using 0.1% formic acid. Separation was achieved on a Synergy Polar-RP reversed phase column (50 × 4.6 mm, 2.5 μm) in gradient elution using a mobile phase composed of water and 0.1% formic acid and a mixture of methanol and acetonitrile (50:50, v/v) containing 0.1% formic acid at a flow rate of 1.0 mL/min. The linear range covered concentrations from 0.273 to 52.6 ng/mL for adefovir and from 0.539 to 104.2 ng/mL for pitavastatin in human plasma, respectively. The calibration curve for adefovir in urine ranged from 0.104 to 10.0 μg/mL. The weighted linear regression (1/conc 2 ) implied excellent linearity with correlation coefficients ≥0.999., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Dictamnine (4-methoxyfuro[2,3-b]quinolone), a furoquinoline alkaloid of the Rutaceae plant family, has been reported to be a phototoxic and photomutagenic compound, whose exposure can cause carcinogenicity, cytotoxicity, and genotoxicity. Metabolic activation is suggested to play an important role in dictamnine-induced toxicities, and the epoxide metabolite of dictamnine has been reported to be the main intermediate in vitro. The objective of this study was to identify N-acetylcysteine conjugate(s) derived from this reactive dictamnine metabolite in vitro and in vivo. An N-acetylcysteine conjugate of dictamnine was detected in microsomal incubations of dictamnine, as well as bile and urine samples of rats treated with dictamnine. The data obtained from the present work will facilitate the understanding of the mechanism behind dictamnine-induced toxicities., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Three methods were developed and validated for determination of nemonoxacin in human feces and its major metabolite, nemonoxacin acyl-β- d-glucuronide, in human urine and feces. Nemonoxacin was extracted by liquid-liquid extraction in feces homogenate samples and nemonoxacin acyl-β- d-glucuronide by a solid-phase extraction procedure for pretreatment of both urine and feces homogenate sample. Separation was performed on a C18 reversed-phase column under isocratic elution with the mobile phase consisting of acetonitrile and 0.1% formic acid. Both analytes were determined by liquid chromatography-tandem mass spectrometry with positive electrospray ionization in selected reaction monitoring mode and gatifloxacin as the internal standard. The lower limit of quantitation (LLOQ) of nemonoxacin in feces was 0.12 µg/g and the calibration curve was linear in the concentration range of 0.12-48.00 µg/g. The LLOQ of the metabolite was 0.0010 µg/mL and 0.03 µg/g in urine and feces matrices, while the linear range was 0.0010-0.2000 µg/mL and 0.03-3.00 µg/g, respectively. Validation included selectivity, accuracy, precision, linearity, recovery, matrix effect, carryover, dilution integrity and stability, indicating that the methods can quantify the corresponding analytes with excellent reliability. The validated methods were successfully applied to an absolute bioavailability clinical study of nemonoxacin malate capsule., (Copyright © 2014 John Wiley & Sons, Ltd.)

To support clinical pharmacokinetic studies with the anticancer agent E7080 (lenvatinib), liquid chromatography tandem mass spectrometry (LC-MS/MS) methods were developed for the quantification of E7080 and four of its metabolites in human plasma, urine and faeces and of E7080 in whole blood. Cross-analyte interferences between metabolites and parent compound were expected and therefore accounted for early in the method development. Plasma, urine and faeces samples were extracted with acetonitrile. Chromatographic separation was achieved on a 50 mm × 2.1 mm I.D. XTerra MS C18 column, with a 0.2 mL/min flow and gradient elution starting with 100% formic acid in water, followed by an increasing percentage of acetonitrile. Whole blood samples were extracted with diethyl ether and extracts were injected on a 150 mm × 2.1mm I.D. Symmetry Shield RP8 column. Detection was performed using an API3000 triple quadrupole mass spectrometer, with a turbo ion spray interface, operating in positive ion mode. Using 250 μL of plasma, E7080 and its metabolites could be quantified between 0.25 and 50.0ng/mL. The quantifiable ranges of E7080 in whole blood, urine and faeces were 0.25-500 ng/mL, 1.00-500 ng/mL and 0.1-25μg/g, using sample volumes of 250 μL, 200 μL and 250 mg, respectively. Calibration curves in all matrices were linear with a correlation coefficient (r(2)) of 0.994 or better. At the lower limit of quantification, accuracies were within ±20% of the nominal concentration with CV values less than 20%. At the other concentrations the accuracies were within ±15% of the nominal concentration with CV values below 15%. The developed methods have successfully been applied in a mass balance study of E7080., (Copyright © 2012 Elsevier B.V. All rights reserved.)

A sensitive and robust method was developed and validated for the routine identification and quantification of five quinolones in urine samples directly injected into a micellar liquid chromatographic system without any pre-treatment step. Since the simultaneous elution of the five compounds was not resolved, two mobile phases have been proposed: (a) for ciprofloxacin and levofloxacin 0.15M sodium dodecyl sulphate, 12.5% propanol and 0.5% triethylamine at pH 3.0 as the mobile phase and the detector at excitation wavelength 285 nm and emission wavelength 465 nm; and (b) for lomefloxacin, ofloxacin and moxifloxacin 0.05 M sodium dodecyl sulphate, 12.5% propanol and 0.5% triethylamine at pH 3.0 as the mobile phase and the detector at excitation wavelength 295 nm and emission wavelength 485 nm. Using these conditions, and in accordance with the food and drug analysis (FDA) guideline, the limit of quantification was 1 ng/mL, and the relative standard deviation and accuracy of the inter-day assay were 1.0-8.4% and 0.11-1.5%, respectively. Detection of the urinary excretion of four quinolones was followed up at 12h after the healthy volunteers had taken the drug. No potential interference from metabolites was observed. This procedure permits the rapid and reproducible measurement of low levels of quinolones in a small amount of urine.

This paper describes a high-performance liquid chromatographic method for the assay of quinfamide and its main metabolite, 1-(dichloroacetyl)-1,2,3,4,-tetrahydro-6-quinolinol, in plasma, urine and feces. It requires 1 ml of biological fluid, an extraction using Sep-Pack cartridges and acetonitrile for drug elution. Analysis was performed on a CN column (5 microm) using water-acetonitrile-methanol (40:50:10) as a mobile phase at 269 nm. Results showed that the assay was linear in the range between 0.08 and 2.0 microg/ml. The limit of quantitation was 0.08 microg/ml. Maximum assay coefficient of variation was 14%. Recovery obtained in plasma, urine and feces ranged from 82% to 98%.

A rapid, sensitive and selective liquid chromatographic procedure was developed to quantitate the levels of a novel leukotriene D4 antagonist, MK-0571 (I), in biological samples. The method involves the addition of an internal standard, an analogue of I, and methanol to the biological matrix. Following centrifugation the supernatant is chromatographed isocratically on a C18 reversed-phase column and the acids are detected with an ultraviolet detector. The sensitivity of the method is such that 50 ng of drug can be quantitated per aliquot of sample. Assays were linear over a 0.06-40.0 micrograms range and exhibited a recovery of 100.5 +/- 7.0% (mean +/- S.D.) over this range. This procedure was utilized to monitor plasma, liver and urinary levels of I in chronic and acute toxicity studies in several animal species.