In spite of the fact that dissolution time profiles of 250mg ursodeoxycholic acid (UCDA) capsules developed by Sponsor and 250mg hard capsules produced by Ursofalk®, Dr. Falk Pharma GmbH, indicated similarity (f2=60.6), a bioavailability study indicated unexpected differences in the formulations. To find an explanation of the in vivo performance of the compared formulations, the dissolution profiles were analyzed using a novel dissolution theory considering: The dissolution model was applied to the measured data using SADAPT. Despite Cmax and AUC values showing higher values after administration of the test product, a reduction of UDCA particle size for the test formulation was suggested for reformulation. The decision was based on the strongly pH-dependent UDCA solubility, formation of insoluble crystals at low pH condition and the known high pH fluctuations ranging from pH1 to 8 in empty stomach. The performed reformulation led to increased dissolution rate of the test product and to a positive bioequivalence study which compared the reformulated test generic formulation with two reference products purchased from two highly regulated markets.
- MeSH
- aplikace orální MeSH
- biologické modely MeSH
- chemické modely MeSH
- dospělí MeSH
- klinické křížové studie MeSH
- koncentrace vodíkových iontů MeSH
- kyselina ursodeoxycholová aplikace a dávkování chemie farmakokinetika MeSH
- lidé MeSH
- plocha pod křivkou MeSH
- potkani inbrední BB MeSH
- tobolky MeSH
- uvolňování léčiv * MeSH
- velikost částic MeSH
- zvířata MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- randomizované kontrolované studie MeSH
A validated, highly sensitive and selective high-pressure liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for the quantitative determination of quetiapine (QUE) in human Na2EDTA plasma with mass spectrometry (MS) detection. Clozapine (CLO) was employed as an internal standard. Samples were extracted using solid phase extraction (SPE). Oasis HLB cartridges and the concentration of quetiapine was determined by isocratic HPLC-MS/MS. The SRM mode was used for MS/MS detection. The method was validated over a concentration range of 1.0-382.2 ng/mL. Inter- and intra-day precision and accuracy of the proposed method were characterized by relative standard deviation (R.S.D.) and the percentage of deviation, respectively; both were lower than 8%. The developed method was employed in the pharmacokinetic study of quetiapine.
- MeSH
- antipsychotika farmakokinetika krev MeSH
- chromatografie kapalinová MeSH
- dibenzothiazepiny farmakokinetika krev MeSH
- hmotnostní spektrometrie MeSH
- kalibrace MeSH
- lidé MeSH
- plocha pod křivkou MeSH
- referenční standardy MeSH
- reprodukovatelnost výsledků MeSH
- řízení kvality MeSH
- stabilita léku MeSH
- terapeutická ekvivalence MeSH
- vysokoúčinná kapalinová chromatografie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- randomizované kontrolované studie MeSH
A validated, highly sensitive, and selective HPLC method with MS-MS detection has been developed for quantitative determination of azithromycin (AZI) in human Na2EDTA plasma. Roxithromycin (ROX) was used as internal standard. Human plasma containing AZI and internal standard was ultrafiltered through Centrifree Micropartition devices and the concentration of AZI was determined by isocratic HPLC-MS-MS. Multiple reaction monitoring mode (MRM) was used for MS-MS detection. The calibration plot was linear in the concentration range 2.55-551.43 ng mL(-1). Inter-day and Intra-day precision and accuracy of the proposed method were characterized by R.S.D and percentage deviation, respectively; both were less than 8%. Limit of quantification was 2.55 ng mL(-1). The proposed method was used to determine the pharmacokinetic profile of AZI (250-mg tablets).
- MeSH
- antibakteriální látky chemie krev MeSH
- azithromycin krev MeSH
- časové faktory MeSH
- EDTA krev MeSH
- hmotnostní spektrometrie metody MeSH
- lidé MeSH
- referenční hodnoty MeSH
- reprodukovatelnost výsledků MeSH
- roxithromycin chemie MeSH
- senzitivita a specificita MeSH
- ultrafiltrace MeSH
- vysokoúčinná kapalinová chromatografie metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- validační studie MeSH
