Journal of pharmaceutical and biomedical analysis
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J Pharm Biomed Anal · Aug 2018
Synthetic cannabinoid BB-22 (QUCHIC): Human hepatocytes metabolism with liquid chromatography-high resolution mass spectrometry detection.
Clandestine laboratories continue producing new synthetic cannabinoids that mimic and magnify natural cannabinoids effects to circumvent drug scheduling legislation. New synthetic cannabinoids are highly potent and responsible for many acute intoxications and deaths. Characterization of metabolic pathways is critical to identify metabolite markers whose detection can prove intake. ⋯ Hydrolysis of biological samples before analysis is strongly suggested to improve detection of phase I metabolites. BB-22 3-carboxyindole is not specific for BB-22 intake, as it was previously detected as a minor MDMB-CHMICA and ADB-CHMICA metabolite. Consumption of these two synthetic cannabinoids should be ruled out to confirm BB-22 intake.
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J Pharm Biomed Anal · Mar 2018
Determining particle size and water content by near-infrared spectroscopy in the granulation of naproxen sodium.
Near-infrared spectroscopy is frequently used by the pharmaceutical industry to monitor and optimize several production processes. In combination with chemometrics, a mathematical-statistical technique, the following advantages of near-infrared spectroscopy can be applied: It is a fast, non-destructive, non-invasive, and economical analytical method. One of the most advanced and popular chemometric technique is the partial least square algorithm with its best applicability in routine and its results. ⋯ The following influences should be considered for application in routine production: constant changes in water content up to 21% and a product temperature up to 54 °C. The different stages of optimization result in a "Root Mean Square Error" of 2.54% for the calibration data set and 3.53% for the validation set by using the Kubelka-Munk conversion and first derivative for the near-infrared spectroscopy method for a particle size >63 μm. For the near-infrared spectroscopy method using a particle size >100 μm, the "Root Mean Square Error" was 3.47% for the calibration data set and 4.51% for the validation set, while using the same pre-treatments. - The robustness and suitability of this methodology has already been demonstrated by its recent successful implementation in a routine granulate production process.
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J Pharm Biomed Anal · Feb 2018
High throughput μ-SPE based elution coupled with UPLC-MS/MS for determination of eluxadoline in plasma sample: Application in pharmacokinetic characterization of PLGA nanoparticle formulations in rats.
Eluxadoline is a novel μ- and κ-opioid receptor (OR) agonist and δ-OR antagonist, recently approved as a first line therapy for the treatment of irritable bowel syndrome. Due to abuse potential, poor bioavailability and high intersubject variability, a sensitive and reliable assay is prerequisite for its determination in biological samples. This work first time report the development and validation of UPLC-MS/MS assay for determination of eluxadoline in rat plasma sample using risperidone as an internal standard (IS). ⋯ The calibration curves were linear in concentration range of 0.15-50ngmL-1 with LOD and LOQ of 0.07 and 0.15ngmL-1, respectively. The validation results satisfied the criteria of USFDA and SWGTOX guidelines and were within the acceptable limit. Finally, the method was successfully applied in bioavailability enhancement study of the newly developed PLGA nanoparticles and Eudragit coated PLGA nanoparticles of eluxadoline in rats.
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J Pharm Biomed Anal · Jan 2018
Physicochemical stability and aerosolization performance of dry powder inhalation system containing ciprofloxacin hydrochloride.
Antibiotic delivery in form of dry powder inhalation has been studied for possible clinical treatment of respiratory tract infection in the recent years. Dry powder inhalation of ciprofloxacin hydrochloride (CIP) assures local antibacterial activity and comfort of easy application. The aim of this work was to test the stability of co-spray-dried CIP in carrier free system. ⋯ In relation to fine particle fraction and mass median aerodynamic diameter (determining the aerosolization parameters), it was found that the particle size and particle shape did not show significant changes after the storage. Among the excipients LEU was found to have many advantages, including relatively simple formulation, enhanced aerosolization behaviour, convenient portability and inherently improved stability. Such a composition may serve as an innovative drug delivery system for the local treatment of respiratory tract infection and cystic fibrosis.
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J Pharm Biomed Anal · May 2017
Quantitative chiral and achiral determination of ketamine and its metabolites by LC-MS/MS in human serum, urine and fecal samples.
Ketamine (KET) is a widely used anesthetic drug which is metabolized by CYP450 enzymes to norketamine (n-KET), dehydronorketamine (DHNK), hydroxynorketamine (HNK) and hydroxyketamine (HK). Ketamine is a chiral compound and S-ketamine is known to be the more potent enantiomer. Here, we present the development and validation of three LC-MS/MS assays; the first for the quantification of racemic KET, n-KET and DHNK in human serum, urine and feces; the second for the separation and quantification of the S- and R-enantiomers of KET, n-KET and DHNK, and the third for separation and quantification of 2S,6S-hydroxynorketamine (2S,6S-HNK) and 2R,6R-hydroxynorketamine (2R,6R-HNK) in serum and urine with the ability to separate and detect 10 additional hydroxylated norketamine metabolites of racemic ketamine. ⋯ The assays were successfully validated according to current bioanalytical guidelines and applied to a pilot study in one healthy volunteer. Compared to previously published methods, our assays have superior analytical features such as a lower amount of required matrix, faster sample preparation, shorter analytical run time and higher sensitivity (LLOQ up to 0.1ng/ml). Moreover, our assay enables for the first time the enantioselective determination of 2R,6R- and 2S,6S-HNK which were shown to be responsible for the promising antidepressant effects of ketamine.