Food does not affect the pharmacokinetics of tesaglitazar, a novel dual peroxisome proliferator-activated receptor alpha/gamma agonist.

Tesaglitazar is a dual peroxisome proliferator-activated receptor (PPAR) alpha/gamma agonist in development to treat lipid and glucose abnormalities associated with type 2 diabetes. This study evaluated the effects of food on tesaglitazar pharmacokinetics. In an open, randomized, 2-way crossover study, 20 healthy men received tesaglitazar 1 mg during fasting and after a high-fat, high-calorie breakfast. Blood samples were taken to assess pharmacokinetic variables. Systemic exposure to tesaglitazar was unaffected by food intake. Estimated ratios were 0.99 (90% confidence interval [CI], 0.94-1.04) for fed/fasted area under plasma concentration-time curve and 0.82 (90% CI, 0.78-0.86) for fed/fasted maximum plasma concentration (C(max)). Mean C(max) was approximately 18% lower (0.41 [95% CI, 0.38-0.43] versus 0.50 [95% CI, 0.47-0.53] mumol/L), and median time to C(max) was increased (2.00 vs 0.75 h) in fed versus fasted state. The median difference of t(max) was 1.25 h (P = .0001, signed-rank test). Tesaglitazar was well tolerated. Tesaglitazar pharmacokinetics is unaffected by food intake, allowing once-daily administration of tesaglitazar with or without food in clinical practice.

Determination of the enantiomers of omeprazole in blood plasma by normal-phase liquid chromatography and detection by atmospheric pressure ionization tandem mass spectrometry.

An enantioselective assay of omeprazole in blood plasma using normal-phase liquid chromatography on a Chiralpak AD column and detection by mass spectrometry is described. Omeprazole is extracted by a mixture of dichloromethane and hexane and, after evaporation, redissolution and injection, separated into its enantiomers on the chiral stationary phase. Detection is made by a triple quadrupole mass spectrometer, using deuterated analogues as internal standards. The method enables determination in plasma down to 10 nmol/l (LOQ) and shows excellent consistency suited for pharmacokinetic studies in man.

Determination of candesartan cilexetil, candesartan and a metabolite in human plasma and urine by liquid chromatography and fluorometric detection.

Liquid chromatographic methods are described for the determination of a new effective anti-hypertensive drug candesartan (CV-11974), its prodrug candesartan cilexetil (TCV-116) and a metabolite, CV-15959 in human plasma and urine. The assays comprise liquid-liquid extraction and separation on a phenyl column with fluorometric detection. The methods give absolute recoveries of 70, 83 and 78% for candesartan cilexetil, candesartan and CV-15959, respectively, and the limit of quantification is 5, 1 and 3 nM of plasma (RSD < 20%), respectively. The methods were applied to plasma and urine samples from biopharmaceutical and clinical studies in man.

Determination of an ultrashort-acting antihypertensive dihydropyridine, clevidipine, in blood using capillary gas chromatography-mass spectrometry and of the primary metabolite using liquid chromatography and fluorescence detection.

A method for the quantitative determination of a new ultrashort-acting dihydropyridine, clevidipine (butyroxymethyl methyl 4-(2',3'-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxyl ate), in whole blood with capillary gas chromatography-mass spectrometry with negative ion chemical ionisation is presented. The rapidly metabolised drug is stabilised in blood using sodium dodecyl sulphate (SDS) which prevents ester hydrolysis. The analytical procedure involves liquid-liquid extraction prior to gas chromatographic determination with a limit of quantification of 0.5 nmol/l blood. The acidic primary metabolite (methyl 4-(2',3'-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxyl ate), MI, can be determined with liquid chromatography and fluorescence detection using a similar sample work-up procedure. Ascorbic acid is then added before sampling to prevent oxidation. The limit of quantification for MI is 50 nmol/l blood.