Determination of the enantiomers of thioridazine, thioridazine 2-sulfone, and of the isomeric pairs of thioridazine 2-sulfoxide and thioridazine 5-sulfoxide in human plasma

Eap, Chin B.; Koeb, L.; Powell, Kerry; Baumann, Pierre

doi:10.1016/0378-4347(95)00096-2

Cited by 39 publications

(37 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…2). This result was in agreement with that of Eap et al, 1 which indicates that a commercially supplied sample of MES (as the besylate) consisted almost entirely of one diastereoisomeric pair of enantiomers.…”

Section: Nmr Studies Of Commercially Obtainedsupporting

confidence: 92%

“…Additionally, it might be expected that there should be a clear difference in the diastereoisomeric ratio of MES (87:13), as reported by Eap et al 1 Initially, few of the protons in the NMR spectrum of MES appeared to show any evidence of diastereotopic resolution, i.e., no peak separation. However, upon closer examination of the N-methyl proton peak diastereotopic resolution could be observed, and this indicated a difference in the diastereoisomeric ratio (91.5:8.5%) (Fig.…”

Section: Nmr Studies Of Commercially Obtainedmentioning

confidence: 75%

“…However, it is not clear whether these authors achieved the separation of the two diastereoisomers of MES or of one enantiomeric pair of MES, as they made no reference to the specifics of the chiral separation they had accomplished, or to the fact that MES existed as four diastereoisomers. Also, there has only been one report, by Eap et al, 1 of the separation of all four stereoisomers of MES on a Chiralpak AS column. However, this report showed that the MES sample (mesoridazine besylate salt) supplied by Sandoz Pharmaceuticals (East Hanover, NJ) was comprised almost entirely of one diastereoisomeric pair of enantiomers ( f 87%).…”

mentioning

confidence: 99%

“…Furthermore, the latest edition of the USP monograph for MES does not mention any specific indications in relation to the diastereoisomeric ratio of MES besylate. 11 Due to the reported discrepancy by Eap et al, 1 and the lack of available information regarding the enantiomeric composition of MES, a novel NMR approach was adopted for the diastereotopic and enantiomeric analysis of MES. These studies involved the analysis of a sample of mesoridazine besylate obtained commercially from Biomol Pharmaceuticals (Plymouth Meeting, PA), and of a freshly synthesised sample of MES prepared by the direct oxidation of rac-THD.…”

mentioning

confidence: 99%

See 3 more Smart Citations

Diastereotopic analysis of mesoridazine besylate (serentil)

Morrow

Millership²,

Collier³

2004

Chirality

View full text Add to dashboard Cite

NMR studies were conducted with the aim of determining the diastereoisomeric ratio of a commercially supplied sample of mesoridazine (MES) and to compare the results with a freshly synthesised sample of MES. The results indicated that the commercially supplied MES consisted almost entirely of one diastereoisomeric pair, which was in agreement with previous findings reported by Eap et al. The synthesised sample of MES was analysed by NMR in two stages: 1) as the initial product isolated as the free base from the direct synthesis, and 2) as the free base isolated from the crystallised besylate salt of the synthetic product. The NMR results show that the initial synthetic product consisted of two equal pairs of diastereoisomers. The diastereoisomeric pairs were further separated by the addition of the chiral shift reagent (R)-(-)-N-(3,5 dinitrobenzoyl)-alpha-benzylamine to reveal equal quantities of all four enantiomers, clearly observed at the methyl sulfoxide proton peak of the NMR scan. The sample obtained from the crystallisation of MES besylate, however, indicated a significant difference, with a diastereoisomeric ratio of 75:25. The results suggest that MES besylate undergoes preferential crystallisation of one pair of diastereoisomers, with the other pair remaining in solution.

show abstract

Section: Nmr Studies Of Commercially Obtainedsupporting

confidence: 92%

Section: Nmr Studies Of Commercially Obtainedmentioning

confidence: 75%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Diastereotopic analysis of mesoridazine besylate (serentil)

Morrow

Millership²,

Collier³

2004

Chirality

View full text Add to dashboard Cite

show abstract

“…Thioridazine 7 is a phenothiazine neuroleptic drug for the treatment of schizophrenia and other psychiatric disorders [93]. Lin et al [94] studied the enantiomerization of thioridazine 7 in dependency of the chiral selector used to separate the enantiomers.…”

Section: Drugsmentioning

confidence: 99%

Investigation of the stereodynamics of molecules and catalyzed reactions by CE

Trapp

2010

Electrophoresis

View full text Add to dashboard Cite

The investigation of the molecular dynamics of stereoisomers and the study of the kinetics of reactions, in particular of catalyzed reactions, is of fundamental interest in chemistry, biochemistry, and medicine. Understanding how to control the transition state of a reaction allows for a directed design of new catalysts and benign processes. The integration of reactions and capillary or microchip-based electrophoretic separations is highly attractive to perform on-column derivatizations or enzymatic on-column digests of peptides and proteins for further characterization. The present review article focuses on the recent advances to study the stereodynamics of molecules and reaction kinetics of catalyzed processes by means of CE. Models and algorithms to evaluate interconversion profiles obtained by electrophoretic separation techniques are discussed with respect to the challenging demands of high separation efficiencies typical for electrophoretic techniques. Models used for evaluation are based on iterative computer simulation algorithms using the theoretical plate model or stochastic model of chromatography, empirical calculation methods, derived from equations used in chemical engineering, namely Damköhler analysis, and direct access with the approximation function and more recently with the unified equation, which can be applied to all kinds of first-order reactions taking place during a chromatographic or a electrophoretic separation. Furthermore, areas of applications are presented and discussed to give a guideline for using dynamic CE and on-column reaction electrophoresis to study kinetics of reactions and dynamic processes.

show abstract

High performance liquid chromatography/electrospray tandem mass spectrometry for phenothiazines with heavy side chains in whole blood

Seno

Hattori

Ishii

et al. 1999

Rapid Commun. Mass Spectrom.

View full text Add to dashboard Cite

Eleven phenothiazine derivatives with heavy side chains contained in human whole blood have been analyzed by high-performance liquid chromatography (HPLC)/electrospray (ES) tandem mass spectrometry (MS). All compounds gave the base peaks due to [M + 1](+) by HPLC/ES single MS. The product ions formed from each quasi-molecular ion by HPLC/ES tandem MS showed the base peaks due to side chains liberated. The mass chromatography of HPLC/ES tandem MS showed much higher sensitivity than that of HPLC/ES single MS for phenothiazines spiked to whole blood. Therefore, regression equations, detection limits, recovery rates and reproducibility were studied for thiethylperazine, clospirazine and flupentixol spiked to human whole blood by means of mass chromatography of HPLC/ES tandem MS. The three compounds showed good linearity in the range of 2-40 ng/mL with a detection limit of about 0.5 ng/mL. Recoveries of the three compounds spiked to whole blood (2 and 8 ng added to 1 mL whole blood) were 43.4-72.5 %; the coefficients of intraday and interday variations were 3.7-9.3 and 12.6-17.9 %, respectively. Thiethylperazine, clospirazine and flupentixol in whole blood could actually be determined with sufficient sensitivity 3 and 6 h after oral administration of 5-10 mg of each compound in a volunteer.

show abstract

Determination of the enantiomers of thioridazine, thioridazine 2-sulfone, and of the isomeric pairs of thioridazine 2-sulfoxide and thioridazine 5-sulfoxide in human plasma

Cited by 39 publications

References 12 publications

Diastereotopic analysis of mesoridazine besylate (serentil)

Diastereotopic analysis of mesoridazine besylate (serentil)

Investigation of the stereodynamics of molecules and catalyzed reactions by CE

High performance liquid chromatography/electrospray tandem mass spectrometry for phenothiazines with heavy side chains in whole blood

Contact Info

Product

Resources

About