Abstract：
:Metabolism of the tricyclic azaphenothiazine neuroleptic drug prothipendyl was investigated with in vitro studies using human liver microsomes but also specific isoforms of cytochrome P450 (CYP) enzymes. Identification and analysis of metabolites was done by liquid chromatography (LC) coupled with quadrupole time of flight mass spectrometry (LC-QTOF-MS) as well as triple quadrupole mass spectrometry (LC-QQQ-MS). Results of the herein presented study revealed the proof of various demethylated and oxidized metabolites (-CH2, -C2H4, four derivatives of prothipendyl +O and three derivatives of prothipendyl -CH2+O). Metabolic reactions of prothipendyl were mainly catalyzed by CYP enzymes CYP1A2, CYP2D6, CYP2C19 and CYP3A4. N-demethyl-prothipendyl was predominantly formed by isoforms CYP2C19 and CYP1A2, while particularly the CYP isoenzyme 3A4 was responsible for the formation of prothipendyl sulfoxide. To confirm the formation of previously identified metabolites in vivo, cardiac blood samples that were tested positive for prothipendyl during routine drug testing and serum and urine samples, collected after a voluntary intake of prothipendyl, were analyzed by LC-QQQ-MS. All metabolites of prothipendyl were proven in these authentic specimens. Neither in serum samples nor in urine samples, a prolonged detectability of metabolites in comparison to prothipendyl could be demonstrated.
journal_name
J Pharm Biomed Analjournal_title
Journal of pharmaceutical and biomedical analysisauthors
Krämer M,Broecker S,Madea B,Hess Cdoi
10.1016/j.jpba.2017.07.011subject
Has Abstractpub_date
2017-10-25 00:00:00pages
517-524eissn
0731-7085issn
1873-264Xpii
S0731-7085(17)30824-5journal_volume
145pub_type
杂志文章abstract：:A high performance liquid chromatography (HPLC) method for the detection of traces of LpHse (4-tert-amylphenol and 2-phenylphenol) has been developed and validated. The method was shown to be linear in the range from 0.5 to 10.00 ppm in solution. The method was also shown to be accurate with a recovery of up to 95% by...
journal_title：Journal of pharmaceutical and biomedical analysis
pub_type： 杂志文章
doi：10.1016/j.jpba.2005.10.049
更新日期：2006-05-03 00:00:00
abstract：:A new, rapid and simple method is described and applied to resolve and quantify mixtures of prednisolone acetate, sulfacetamide and phenylefrine. The determination was accomplished by micellar electrokinetic capillary chromatography (MEKC) using a fused silica capillary (57 cm x 75 microm ID). The separation was carri...
journal_title：Journal of pharmaceutical and biomedical analysis
pub_type： 杂志文章
doi：10.1016/s0731-7085(02)00666-0
更新日期：2003-04-01 00:00:00
abstract：:A new extraction technique based on the off-line combination of pressurized-liquid with solid-phase extraction (PLE-SPE) is described. The method was used for the extraction of bioactive phenolic acids (protocatechuic, p-hydroxybenzoic, 2,3-dihydroxybenzoic, chlorogenic, vanillic, caffeic, p-coumaric, salicylic acid),...
journal_title：Journal of pharmaceutical and biomedical analysis
pub_type： 杂志文章
doi：10.1016/j.jpba.2009.03.027
更新日期：2010-01-20 00:00:00
abstract：:The risk assessment of di(2-ethylhexyl) phthalate (DEHP) that migrated from polyvinyl chloride (PVC) medical devices is an important issue for hospitalized patients. Many studies have been conducted to determine the level of DEHP migration. A recent report has indicated that DEHP in blood bags was hydrolyzed by estera...
journal_title：Journal of pharmaceutical and biomedical analysis
pub_type： 杂志文章
doi：10.1016/j.jpba.2005.06.016
更新日期：2005-10-04 00:00:00
abstract：:Several methods are reported for the simultaneous determination of diazepam and pyridoxine: two graphical methods (zero-crossing and derivative quotient spectra); and two numerical methods (multiple linear regression and partial least-squares regression). The methods have been applied in the concentration ranges 1.4-4...
journal_title：Journal of pharmaceutical and biomedical analysis
pub_type： 杂志文章
doi：10.1016/0731-7085(96)01844-4
更新日期：1996-11-01 00:00:00
abstract：:The analysis of volatile samples is mostly performed by GC. However, its separation power may not be enough for some complex samples. Comprehensive gas chromatography (GC × GC) increases the separation power by means of a second separation dimension. Parallel to the great technological advances realised since the earl...
journal_title：Journal of pharmaceutical and biomedical analysis
pub_type： 杂志文章,评审
doi：10.1016/j.jpba.2019.112817
更新日期：2019-11-30 00:00:00
abstract：:The combination of dispersive liquid-liquid microextraction (DLLME) with capillary electrophoresis (CE) and a time-of-flight mass spectrometer (TOF-MS) was evaluated for the toxicological screening in urine samples. A methodology based on design of experiments (DOE) was implemented to increase the extraction efficienc...
journal_title：Journal of pharmaceutical and biomedical analysis
pub_type： 杂志文章
doi：10.1016/j.jpba.2012.03.036
更新日期：2013-01-25 00:00:00
abstract：:The possibility of the rapid identification of drug related minor components by HPLC/diode-array UV spectroscopy is demonstrated by three examples. Hydroxylated impurities (degradation products) of norgestrel (6 alpha and beta, 10 beta-hydroxy derivatives) were identified on the basis of their UV spectra and retention...
journal_title：Journal of pharmaceutical and biomedical analysis
pub_type： 杂志文章
doi：10.1016/0731-7085(95)01579-5
更新日期：1995-12-01 00:00:00
abstract：:An on-line liquid chromatography-immunochemical detection (LC-ICD) system for the quantification of cytokines in cell extracts has been developed using a post-column continuous-flow reaction detection system using fluorescence labelled antibodies. Cytokines eluting from the micro-HPLC column react with antibodies to f...
journal_title：Journal of pharmaceutical and biomedical analysis
pub_type： 杂志文章
doi：10.1016/s0731-7085(01)00464-2
更新日期：2001-12-01 00:00:00
abstract：:A systematic method in hydrophilic interaction chromatography (HILIC) was developed for the separation of four monophosphate nucleotides using design of experiment (DOE) approaches. Three HPLC parameters, the buffer concentration (ammonium acetate concentration), gradient time, and temperature, were evaluated within t...
journal_title：Journal of pharmaceutical and biomedical analysis
pub_type： 杂志文章
doi：10.1016/j.jpba.2018.05.014
更新日期：2018-09-05 00:00:00
abstract：:A refined toxic fraction, Fr-2, from the ethanol extract of Aster tataricus roots was obtained by a toxic tracing isolation. The hepatotoxic effects of Fr-2 were proved by the level elevation of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) in mice serum and further co...
journal_title：Journal of pharmaceutical and biomedical analysis
pub_type： 杂志文章
doi：10.1016/j.jpba.2012.04.034
更新日期：2012-08-01 00:00:00
abstract：:In this article the merits of current liquid chromatography (LC) columns and techniques are reviewed, to include the following topics: (1) a brief introduction to rational therapeutic drug monitoring (TDM) to justify drug measurements; (2) selected recent survey results from the College of American Pathologists (CAP) ...
journal_title：Journal of pharmaceutical and biomedical analysis
pub_type： 杂志文章,评审
doi：10.1016/0731-7085(89)80041-x
更新日期：1989-01-01 00:00:00
abstract：:The chemical stability of 2',3'-dideoxyinosine has been studied over a wide pH range (0-12). A stability-indicating HPLC method was used to separate the degradation product from the parent drug. The effects of temperature, ionic strength and buffer components on the degradation kinetics were investigated. Furthermore,...
journal_title：Journal of pharmaceutical and biomedical analysis
pub_type： 杂志文章
doi：10.1016/0731-7085(93)80162-t
更新日期：1993-06-01 00:00:00
abstract：:A sensitive reverse phase high performance liquid chromatography-electrospray ionization-mass spectrometry (RP-HPLC-ESI-MS) method has been developed and validated for the determination of hydromorphone in human plasma using naloxone as the internal standard (IS). After alkalization with saturated sodium bicarbonate, ...
journal_title：Journal of pharmaceutical and biomedical analysis
pub_type： 杂志文章
doi：10.1016/j.jpba.2011.11.012
更新日期：2012-03-05 00:00:00
abstract：:A high performance liquid chromatographic method was developed to simultaneously determine the 12 major constituents of Forsythia suspensa, namely R-suspensaside, S-suspensaside, S-suspensaside methyl ether, (+)-pinoresinol-beta-d-glucoside, forsythiaside, (+)-epipinoresinol-4'-O-glucoside, suspensaside A, rutin, phil...
journal_title：Journal of pharmaceutical and biomedical analysis
pub_type： 杂志文章
doi：10.1016/j.jpba.2006.09.033
更新日期：2007-02-19 00:00:00
abstract：:CGS 26214 is a racemic compound having cholesterol-lowering activity in rats, dogs, and monkeys. This compound has two equipotent chiral components CGS 28934(-) and CGS 28935(+). An analytical challenge was to develop a sensitive liquid chromatography/tandem mass spectrometry (LC/MS/MS) method for the analysis of the ...
journal_title：Journal of pharmaceutical and biomedical analysis
pub_type： 杂志文章
doi：10.1016/s0731-7085(00)00364-2
更新日期：2000-09-01 00:00:00
abstract：:A straightforward quantitative method for gas chromatography-mass spectrometry determination of isosorbide 5-mononitrate (IS5MN) and its related impurities such as isosorbide (IS), isosorbide diacetate (ISDA) and isosorbide 2-acetate-5-nitrate (IS2A5N) in raw materials as well as in dosage formulations is developed. T...
journal_title：Journal of pharmaceutical and biomedical analysis
pub_type： 杂志文章
doi：10.1016/s0731-7085(97)00079-4
更新日期：1997-11-01 00:00:00
abstract：:Ligustilide (LIG) is the main active ingredient of Angelica sinensis (Oliv.) Diels and has a neuroprotective effect against ischemic stroke. However, owing to its multi-conjugated unstable structure, the compound has poor drug-forming properties. Therefore, we synthesized highly stable colorless needle crystals (known...
journal_title：Journal of pharmaceutical and biomedical analysis
pub_type： 杂志文章
doi：10.1016/j.jpba.2020.113140
更新日期：2020-04-15 00:00:00
abstract：:Everolimus (Eve) is an immunosuppressive macrolide that is being analyzed in various biological matrices and fluids. Its antitumor activity makes this drug suitable not only for organ transplantation but also for breast cancer treatments. In the attempt to reduce the incidence and severity of its side effects, Eve was...
journal_title：Journal of pharmaceutical and biomedical analysis
pub_type： 杂志文章
doi：10.1016/j.jpba.2020.113644
更新日期：2020-11-30 00:00:00
abstract：:Therapeutic monitoring of the potent, highly lipophilic glucocorticoid, fluticasone propionate (FP), was initially performed by a radioimmunoassay method. However an improved method with a lower limit of quantitation (LLOQ) of at least 25 pg per ml (pg/ml(-1)) was needed to measure the low levels of FP present in huma...
journal_title：Journal of pharmaceutical and biomedical analysis
pub_type： 杂志文章
doi：10.1016/s0731-7085(99)00213-7
更新日期：1999-12-01 00:00:00
abstract：:In order to study 2'-deoxycytidine (2'-dCyd) as a possible prognostic marker in cancer chemotherapy, an enzyme immunoassay (EIA) was developed. 2'-dCyd as a hapten was succinylated and two omicron-monosuccinyl-2'-dCyd's were purified by high performance liquid chromatography and identified by mass spectrometry and 1H-...
journal_title：Journal of pharmaceutical and biomedical analysis
pub_type： 杂志文章
doi：10.1016/s0731-7085(96)01982-6
更新日期：1997-06-01 00:00:00
abstract：:The spectrophotometric determination of trace amounts of diclofenac was carried out by liquid-liquid extraction using acridine yellow with a flow system. The determination of diclofenac sodium in the range of 3-80 micrograms ml-1 was possible with a sampling frequency of 40 samples h-1. The method was satisfactorily a...
journal_title：Journal of pharmaceutical and biomedical analysis
pub_type： 杂志文章
doi：10.1016/s0731-7085(97)00028-9
更新日期：1997-10-01 00:00:00
abstract：:The objective of current study was to develop a validated specific stability indicating reversed-phase liquid chromatographic method for the quantitative determination of levofloxacin as well as its related substances determination in bulk samples, pharmaceutical dosage forms in the presence of degradation products an...
journal_title：Journal of pharmaceutical and biomedical analysis
pub_type： 杂志文章
doi：10.1016/j.jpba.2009.05.038
更新日期：2009-12-05 00:00:00
abstract：:A previously established method for the analysis of chlortetracycline by liquid chromatography using polystyrene-divinylbenzene stationary phases was examined in a multicentre study involving four laboratories and a total of 12 columns. Three chlortetracycline hydrochloride samples were analysed. The main component an...
journal_title：Journal of pharmaceutical and biomedical analysis
pub_type： 杂志文章
doi：10.1016/0731-7085(92)80029-m
更新日期：1992-02-01 00:00:00
abstract：:A rapid and simple reversed-phase high performance liquid chromatography (HPLC) method for the quantitation of colistimethate sodium in pharmaceutical formulations has been developed. The chromatographic separation was performed using a Phenomenex Kinetex XB-C18 column with gradient elution using a mobile phase contai...
journal_title：Journal of pharmaceutical and biomedical analysis
pub_type： 杂志文章
doi：10.1016/j.jpba.2017.04.021
更新日期：2017-08-05 00:00:00
abstract：:The shelf-life of a drug is usually determined by fitting the assayed values of drug potency versus time to a linear least-squares model. In least-squares models, the parameters are estimated by minimizing the sum of squares of the residuals. Shelf-life is estimated as the time corresponding to the intersection point ...
journal_title：Journal of pharmaceutical and biomedical analysis
pub_type： 杂志文章
doi：10.1016/0731-7085(93)80078-f
更新日期：1993-09-01 00:00:00
abstract：:A liquid chromatography (LC) method for the determination of ibuprofen in dog plasma is described. Chromatographic separation was performed on a Diamonsil C18 column with a C18 guard column using a binary mixture of acetonitrile and 0.02 mol/l phosphate buffer (pH 6.5) (35:65, v/v) delivered at a flow rate of 1.2 ml/m...
journal_title：Journal of pharmaceutical and biomedical analysis
pub_type： 杂志文章
doi：10.1016/j.jpba.2005.02.013
更新日期：2005-07-15 00:00:00
abstract：:Biosensors containing cytochrome P450cam in a didodecyldimethylammonium bromide vesicular system were prepared by cross-linking onto a glassy carbon electrode (GCE) with glutaraldehyde in the presence of bovine serum albumin. Cyclic voltammetric responses of the sensor in air-free buffer solution showed that the senso...
journal_title：Journal of pharmaceutical and biomedical analysis
pub_type： 杂志文章
doi：10.1016/s0731-7085(98)00076-4
更新日期：1998-09-01 00:00:00
abstract：:A study was carried out to investigate compatibility of atenolol, a beta(1) blocker, with a variety of pharmaceutical excipients. The binary mixtures (1:1) of atenolol with the excipients were stored for 1 month at 40 degrees C/75% RH. The samples were directly observed for the physical changes, and also analyzed by a...
journal_title：Journal of pharmaceutical and biomedical analysis
pub_type： 杂志文章
doi：10.1016/j.jpba.2009.01.014
更新日期：2009-05-01 00:00:00
abstract：:A novel stability-indicating high-performance liquid chromatographic assay method was developed and validated for docetaxel in the presence of degradation products generated from forced decomposition studies. A gradient HPLC method was developed to separate the drug from the degradation products, using a Hichrom RPB H...
journal_title：Journal of pharmaceutical and biomedical analysis
pub_type： 杂志文章
doi：10.1016/j.jpba.2006.01.011
更新日期：2006-05-03 00:00:00
