Detection of Anti-Ulcer Drugs and Their Metabolites in Horse Urine by Liquid Chromatography – Mass Spectrometry

This paper describes a convenient method for the extraction and detection of eight anti-ulcer drugs simultaneously in horse urine, a relatively complex and viscous matrix, using a single-step liquid-liquid extraction followed by high-performance liquid chromatography – mass spectrometry (LC-MS). Anti-ulcer drugs were isolated from horse urine by salting out and liquid-liquid extraction. Detection of these drugs at concentrations below 1 ng mL^?1 could be achieved using LC-MS-MS in the positive atmospheric pressure chemical ionisation (APCI) mode. The above analysis was also extended to elimination studies of horses administered with ranitidine and omeprazole. The urinary elimination data of these two drugs suggest that ranitidine was eliminated from horse urine at a much slower rate than omeprazole. In addition, three ranitidine metabolites and six omeprazole metabolites were identified for the first time in equine urine samples.     

Determination and pharmacokinetic profile of omeprazole in rat blood, brain and bile by microdialysis and high-performance liquid chromatography

The disposition and biliary excretion of omeprazole was investigated following i.v. administration to rats at 10 mg/kg. We used a microdialysis technique coupled to a validated microbore HPLC system to monitor the levels of protein-unbound omeprazole in rat blood, brain and bile, constructing the relationship of the time course of the presence of omeprazole. Microdialysis probes were simultaneously inserted into the jugular vein toward right atrium, the brain striatum and the bile duct of the male Sprague-Dawley rats for biological fluid sampling after the administration of omeprazole (10 mg/kg) through the femoral vein. The concentration-response relationship from the present method indicated linearity (r2>0.995) over a concentration range of 0.01-50 microg/ml for omeprazole. Intra-assay and inter-assay precision and accuracy of omeprazole fell well within the predefined limits of acceptability. Following omeprazole administration, the blood-to-brain coefficient of distribution was 0.15, which was calculated as the area under the concentration versus time curve (AUC) in the brain divided by the AUC in blood (k=AUCbrain/AUCblood). The blood-to-bile coefficient of distribution (k=AUCbile/AUCblood) was 0.58. The decline of unbound omeprazole in the brain striatum, blood and bile fluid suggests that there was rapid exchange and equilibration between the compartments of the peripheral and central nervous systems. In addition, the results indicated that omeprazole was able to penetrate the blood-brain barrier and undergo hepatobiliary excretion.     

Reversed-phase high performance liquid chromatographic method for the determination of lansoprazole, omeprazole and pantoprazole sodium sesquihydrate in presence of their Acid-induced degradation products

A simple sensitive, selective and accurate reversed-phase high performance liquid chromatographic method was developed and validated for the quantitative determination of lansoprazole, omeprazole and pantoprazole sodium sesquishydrate in the presence of their acid-induced degradation products. The three compounds were monitored at 280 nm using Nova-Pak C(18) column and a mobile phase consisting of 0.05 M potassium dihydrogen phosphate : methanol : acetonitrile (5 : 3 : 2 v/v/v). Linearity ranges were 2-20 mug ml(-1), 2-36 mug ml(-1) and 0.5-20 mug ml(-1) for lansoprazole, omeprazole and pantoprazole, respectively. The corresponding recoveries were 100.61+/-0.84%, 100.50+/-0.80% and 99.78+/-0.88%. The minimum detection limits were 0.55, 0.54 and 0.03 mug ml(-1) for lansoprazole, omeprazole and pantoprazole, respectively. The method could be successfully applied to the determination of pure, laboratory prepared mixtures and pharmaceutical dosage forms. The results obtained were compared with the reported methods for lansoprazole and pantoprazole or the official U.S.P method for omeprazole.     

奥美拉唑、兰索拉唑对映体及相关物质在不同手性柱的分离比较

考察了奥美拉唑、兰索拉唑对映体及其拆分剂联二萘酚在4种手性柱（chiralcel OD、chiralpak AD、kromasil CHI-TBB和chiral-AGP)上的色谱行为。实验结果表明：Chiralpak AD、 Chiral-AGP柱分离度大，柱效稳定，并且这两种柱子的配合使用实现了对包结拆分的全过程监控。此外，本文根据对映体在不同手性柱的出峰顺序进行了讨论。     

Continuous permeation of analytes through a thin poly(dimethylsiloxane) membrane followed by sorbent trapping for their gas chromatographic monitoring

Omeprazole is a benzimidazole compound that acts as a proton-pump inhibitor. Because the metabolism of omeprazole is mainly catalyzed by cytochrome P-450 (CYP) 3A4 and CYP2C19. the genetic polymorphism of CYP2C19 could be of clinical concern in the treatment of acid-related diseases with omeprazole. Therefore, a reliable method for omeprazole phenotyping is desirable in clinical situations. This study has demonstrated the determination of omeprazole and its metabolites in human plasma by liquid chromatography-three-dimensional quadrupole mass spectrometry with a sonic spray ionization interface. The analytical column was YMC-Pack Pro C18(50x2.0 mm I.D.) using acetonitrile-50 mM ammonium acetate (pH 7.25) (1:4) at a flow-rate of 0.2 ml/min. The drift voltage was 30 V. The sampling aperture was heated at 110 degrees C and Shield temperature was 230 degrees C. In the mass spectrum, the molecular ions of omeprazole, hydroxyomeprazole and omeprazole sulfone were clearly observed as base peaks. This method is sufficiently sensitive and accurate for pharmacokinetic studies of omeprazol.     

Resolution of the enantiomers of omeprazole and some of its analogues by liquid chromatography on a trisphenylcarbamoylcellulose-based stationary phase. The effect of the enantiomers of omeprazole on gastric glands

The enantiomers of omeprazole and some of its analogues have been separated on a chiral stationary phase comprising trisphenylcarbamoylcellulose coated on 3-aminopropyl silica. The nature of the supporting silica has a crucial effect on the separations obtained. The racemisation half-life of omeprazole was estimated to be 1.3.10(2) h at 37 degrees C. In vitro tests on isolated gastric glands from rabbits showed that both enantiomers of omeprazole had an inhibitory effect on acid formation.     

Investigating the presence of omeprazole in waters by liquid chromatography coupled to low and high resolution mass spectrometry: degradation experiments

Omeprazole is one of the most consumed pharmaceuticals around the world. However, this compound is scarcely detected in urban wastewater and surface water. The absence of this pharmaceutical in the aquatic ecosystem might be due to its degradation in wastewater treatment plants, as well as in receiving water. In this work, different laboratory‐controlled degradation experiments have been carried out on surface water in order to elucidate generated omeprazole transformation products (TPs). Surface water spiked with omeprazole was subjected to hydrolysis, photo‐degradation under both sunlight and ultraviolet radiation and chlorination. Analyses by liquid chromatography coupled to quadrupole time‐of‐flight mass spectrometry (LC–QTOF MS) permitted identification of up to 17 omeprazole TPs. In a subsequent step, the TPs identified were sought in surface water and urban wastewater by LC–QTOF MS and by LC coupled to tandem mass spectrometry with triple quadrupole. The parent omeprazole was not detected in any of the samples, but four TPs were found in several water samples. The most frequently detected compound was OTP 5 (omeprazole sulfide), which might be a reasonable candidate to be included in monitoring programs rather than the parent omeprazole. Copyright © 2013 John Wiley & Sons, Ltd.     

原位制备8-氘代奥美拉唑钠

奥美拉唑分子中的氮原子质子化,对邻近的碳核产生有效的电四极矩驰豫,使邻近碳核信号加宽或消失,以致奥美拉唑在DMSO-d6或DMSO-d6/D2O溶液中的碳谱(13CNMR、DEPT-90、DEPT-135)及碳-氢相关谱(HMQC、HMBC)具有非典型的特征,即部分碳原子不出峰且峰形很差,以致无法确定具体的碳数,延长脉冲重复时间无改观。本实验通过将奥美拉唑与NaOH的D2O溶液反应原位制备8-氘代奥美拉唑钠,使吡啶氮原子去质子化,从而使部分不出峰的碳核信号变窄或重又出现,顺利地完成了8-氘代奥美拉唑钠上述谱图的采集,间接地解决了奥美拉唑的碳谱分析,因而提供了一种可通用的测试苯骈咪唑类质子泵抑制剂碳谱及其二维相关谱的方法。     

Triarylborane-Appended Anils and Boranils: Solid-State Emission,Mechanofluorochromism, and Phosphorescence

Herein, the design, synthesis, optical properties, and mechanofluorochromism characteristics of a series of conjugates having covalently linked triarylborane (TAB) and anil/boranil units (TAB-anil: 1 a – 3 a and TAB-boranil: 1 – 3 ) are reported. The electronic interactions between TAB and anil/boranil in 1 a – 3 a and 1 – 3 were fine-tuned by changing the boryl moiety's position on the phenyl spacer connecting the BMes₂ (Mes=mesityl) and anil/boranil units. A boryl moiety at the meta position ( 1 a ) of the phenyl spacer stabilizes the enolic form (E-OH), whereas a boryl moiety at the para position ( 2 a and 3 a ) stabilizes the keto form (Z-NH) in the solid state. However, in solution 1 a , 2 a , and 3 a exhibit keto–enol tautomerism in both ground and excited states. Compounds 1 a – 3 a and 1 – 3 show red-shifted absorption compared with 4 a and 4 , which are devoid of TAB moieties, which indicate effective participation of an empty p orbital on the boron center in 1 a – 3 a and 1 – 3 . Compounds 1 and 2 showed fluorescence variations in response to external stimuli such as mechanical grinding. Long phosphorescence lifetimes of 18–46 ms were observed for compounds 1 – 3 . The observed optical properties of 1 a – 3 a and 1 – 3 are rationalized in the context of quantum mechanical calculations.     

Densitometric HPTLC Analysis of Juglone,Quercetin, Myricetin,Rutin, Caffeic Acid,and Gallic Acid in Juglans regia L.

JPC – Journal of Planar Chromatography – Modern TLC - Asensitive, selective, and precise high-performance thin-layer chromatography (HPTLC) method was developed for simultaneous...     

Apical acidity decreases inhibitory effect of omeprazole on Mg2+ absorption and claudin-7 and -12 expression in Caco-2 monolayers

Clinical studies reported hypomagnesaemia in long-term omeprazole usage that was probably due to intestinal Mg²⁺ wasting. Our previous report demonstrated the inhibitory effect of omeprazole on passive Mg²⁺ transport across Caco-2 monolayers. The present study aimed to identify the underlying mechanism of omeprazole suppression of passive Mg²⁺ absorption. By using Caco-2 monolayers, we demonstrated a potent inhibitory effect of omeprazole on passive Mg²⁺, but not Ca²⁺, transport across Caco-2 monolayers. Omeprazole shifted the %maximum passive Mg²⁺ transport-Mg²⁺ concentration curves to the right, and increased the half maximal effective concentration of those dose-response curves, indicating a lower Mg²⁺ affinity of the paracellular channel. By continually monitoring the apical pH, we showed that omeprazole suppressed apical acid accumulation. Neomycin and spermine had no effect on passive Mg²⁺ transport of either control or omeprazole treated monolayers, indicating that omeprazole suppressed passive Mg²⁺ transport in a calcium sensing receptor (CaSR)-independent manner. The results of western blot analysis showed that omeprazole significantly suppressed claudin (Cldn)-7 and -12, but not Cldn-2, expression in Caco-2 cells. By using apical solution of pH 5.5, 6.0, 6.5, and 7.0, we found that apical acidity markedly increased passive Mg²⁺ transport, Mg²⁺ affinity of the paracellular channel, and Cldn-7 and -12 expression in Caco-2 monolayers. Apical acidity abolished the inhibitory effect of omeprazole on passive Mg²⁺ transport and Cldn-7 and -12 expression. Our results provided the evidence for the regulation of intestinal passive Mg²⁺ absorption by luminal acidity-induced increase in Cldn-7 and -12 expression.     

A Novel Synthesis of 1-Aryl-9-alkyl-2, 3, 3a, 4, 9, 9a-hexahydro-1H-pyrrolo[2, 3-b] quinoxalines by lithium aluminium hydride reduction of N-phenyl-1-benzimidazolyl-succinimides

The N-substituted 1-benzimidazolyl-succinimides 6a – v (Scheme 1, Table 1 and 2) have been prepared by the reaction of benzimidazole and its derivatives with maleimides. Reduction of the N-cyclohexyl and N-cyclo-octyl substituted 1-benzimidazolyl-succinimides 6i – k with lithium aluminium hydride gives the normally expected substituted (N-alkyl-3-pyrrolidinyl)benzimidazoles 14i – k . However by LiAlH₄-reduction of the N-phenyl substituted 1-benzimidazolylsuccinimides 6a – h mainly the 1-aryl-9-alkyl-2, 3, 3a, 4, 9, 9a-hexahydro-1H-pyrrolo[2, 3-b]quinoxalines 7a – h are obtained. The mechanism of this unusual reduction has been elucidated.     

Stereoselective effects in the separation of enantiomers of omeprazole and other substituted benzimidazoles on different chiral stationary phases

The enantioselective separation of omeprazole on different chiral stationary phases was investigated. The two enantiomers could be resolved on three different phases with immobilized protein, Chiral-AGP, Ultron ES-OVM and BSA-DSC, employing aqueous mobile phases with 2-propanol as organic modifier. On Chiralpak AD, an amylose-based chiral stationary phase, the enantiomers of omeprazole and three analogues could be separated using a non-polar hexane-ethanol mobile phase. For omeprazole the retention order was reversed when 2-propanol was replaced with ethanol or methanol as the modifier of hexane in the mobile phase.     

Mononuclear Tetraamineplatinum(II) Complexes: Synthesis,Anticancer Activity,DNA Binding,and Cellular Uptake

The synthesis of three bis[(tert‐butoxy)carbonyl]‐protected (tetramine)dichloroplatinum complexes 2a – c of formula cis‐[PtCl₂(LL)] and of their cationic deprotected analogs 3a – c and their evaluation with respect to in vitro cytotoxicity, intramolecular stability, DNA binding, and cellular uptake is reported. The synthesis comprises the complexation of K₂[PtCl₄] with di‐N‐protected tetramines 1a – c to give 2a – c and subsequent acidolysis, yielding 3a – c . The cytotoxicity of the complexes is in direct relation to the length of the polyamine. Complexes 3a – c display a significant higher affinity for CT DNA as well as for cellular DNA in A2780 cells than cisplatin.     

New insight into the discrimination between omeprazole enantiomers by cyclodextrins in aqueous solution

We report results regarding the use of ¹H-NMR spectroscopy in the study of the conformational behaviour and optical activity of omeprazole. Changes in the chemical shifts of chosen atoms reveal that the conformational behaviour of omeprazole is temperature and pH sensitive. Separation and identification of omeprazole enantiomers in the presence of natural and derivative cyclodextrins, such as β-cyclodextrin (βCD) and methyl-β-cyclodextrin (MβCD) are achieved using ¹H-NMR spectroscopy, with information from molecular dynamics simulation. This work shows that βCD includes preferentially R-(–)-omeprazole, acting as a chiral selector. This discrimination of omeprazole enantiomers by cyclodextrins allows development of pharmaceutical formulations with a better bioavailability profile.     

Densitometric Determination of Naproxen,and of Naproxen Methyl Ester,its Impurity,in Pharmaceutical Preparations

JPC – Journal of Planar Chromatography – Modern TLC - A chromatographic–densitometric method has been established for identification and quantification of...     

Thin-Layer Chromatographic Determination of Diazepam,Phenobarbitone, and Saccharin in Toddy Samples

JPC – Journal of Planar Chromatography – Modern TLC -     

Synthesis of Novel Chromene,Pyridine, Pyrazole,Pyrimidine, and Imidazole Derivatives via One‐pot Multicomponent Reaction

New series of chromenes 2 – 4 , pyridines 5 – 8 , and pyranopyrazoles 9a,b were synthesized via one‐pot multicomponent reaction of 4‐tosyloxybenzaldehyde ( 1 ) and malononitrile with phenols, amines or hydrazines, and ethyl acetoacetate, respectively. Compound 9a was reacted with acetic anhydride, formic acid, or formamide to afford N ‐acetyl derivative 10 and pyrazolopyranopyrimidines 11 – 13 , respectively. Imidazole derivatives 14 and 15a – d were obtained by multicomponent reaction between compound 1 with ammonium acetate and benzil or aromatic amines in (1:2:1) or (1:1:1:1) ratio, respectively. The structures of new compounds were elucidated by elemental and spectral analyses.     

Simultaneous Determination of Marmin,Skimmianine, Umbelliferone,Psoralene, and Imperatorin in the Root Bark of Aegle Marmelos by High-Performance Thin-Layer Chromatography

JPC – Journal of Planar Chromatography – Modern TLC - Aegle marmelos (Rutaceae) has gained traditional therapeutic importance owing to their coumarins (umbelliferone, psoralene, marmin,...     

A New TLC Method for Quantification of Paraquat,Diquat, Difenzoquat,Mepiquat and Chloromequat in Water

JPC – Journal of Planar Chromatography – Modern TLC - We report improved separation of the highly toxic contact herbicides paraquat, diquat, difenzoquat, mepiquat, and chloromequat by...