Food-effect study of nilotinib in chronic myeloid leukaemia (NiFo study): Enabling dose reduction and relief of treatment burden.

Objectives: Taking advantage of its food-dependent bioavailability, the present study investigated the effect of a reduced dose taken with real-life meals on the pharmacokinetics (PK) of nilotinib in chronic myeloid leukaemia (CML) patients.

Methods: Nilotinib was taken fasted (300 mg BID, days 1-4) or with real-life meals (200 mg BID, days 5-11). Rich sampling (days 1, 3, 8, 11) allowed for non-compartmental PK analysis.

An UPLC-MS detection method for the quantification of five antibiotics in human plasma.

Background: An UPLC-MS detection method for the quantification of amikacin, flucloxacillin, meropenem, penicillin G and vancomycin was developed and validated.

Results: The calibration curves were found to be linear from 0.47 to 50 mg/l for amikacin, 1.

Haematocrit corrected analysis of creatinine in dried blood spots through potassium measurement.

We developed a method for the analysis of creatinine in dried blood spot (DBS) samples to facilitate monitoring of renal function in combination with TDM of immunosuppressive drugs for transplant patients outside the hospital. An 8-mm disc of the DBS was punched, extracted and followed by LC-MS/MS analysis. The haematocrit proved to have a significant influence on the analysis of creatinine in DBS samples.

Rapid quantification of gabapentin, pregabalin, and vigabatrin in human serum by ultraperformance liquid chromatography with mass-spectrometric detection.

Background: Gabapentin (GBP), pregabalin (PRG), and vigabatrin (VIG) are used for the prevention and treatment of epileptic seizures. The developed method was applied to samples from subjects participating in a pharmacokinetic study of GBP.

Methods: Sample pretreatment consisted of adding 20 μL of trichloroacetic acid (30%; vol/vol) and 200 μL of GBP-d4 in acetonitrile as an internal standard to 20 μL of serum.

Safety and efficacy of the immunosuppressive agent 6-tioguanine in murine model of acute and chronic colitis.

Background: Oral thiopurines are effective and widely used in treatment of inflammatory bowel disease (IBD) in humans, although their use is limited due the development of adverse events. Here, we examine the efficacy and toxicity of oral treatment with 6-tioguanine (6-TG) and azathioprine (AZA) in a murine model of IBD.

Methods: We induced acute or chronic colitis in BALB/c mice by one or four cycles of 3% dextran sulphate sodium (DSS), respectively.

Validated liquid chromatography-tandem mass spectroscopy method for the simultaneous quantification of four antimycotic agents in human serum.

A liquid chromatography-tandem mass spectrometry method was developed and validated for the simultaneous quantification of voriconazole, fluconazole, posaconazole, itraconazole, and hydroxyitraconazole in human serum. A simple protein precipitation was used as sample pretreatment with ketoconazole as the internal standard. Chromatographic separation was performed on a Waters Alliance 2795 liquid chromatography system using a XBridge RP18 column.

Quantitative analysis of sildenafil and desmethylsildenafil in human serum by liquid chromatography-mass spectrometry with minimal sample pretreatment.

A simple, sensitive and specific liquid chromatography tandem mass spectrometry method with minimal sample pretreatment was developed for the simultaneous analysis of sildenafil and its metabolite desmethylsildenafil in human serum. Sample pretreatment consisted of adding a methanolic solution of the internal standard vardenafil to the samples. After vortexing and centrifugation the samples were directly injected onto the C18 column using gradient elution.