Distinct relations among plasma concentrations required for different pharmacological effects in oxycodone, morphine, and fentanyl.

Several clinical reports showed that adverse effect profiles are not the same in morphine, oxycodone, and fentanyl. The authors investigated whether the relationship between plasma concentrations for antinociceptive effect and for various pharmacological effects differed among oxycodone, morphine, and fentanyl under controlled experimental setting using animal models. Oxycodone induced constipation and an antinociceptive effect in a similar concentration-dependent manner, whereas morphine required approximately 9-fold higher plasma concentration for antinociceptive effect compared with that for constipation when 50% effective plasma concentration (EC(50)) levels were compared.

Development of a rapid and detailed structural identification system with an on-line immobilized enzyme reactor integrated into LC-NMR.

Immobilized enzyme reactors (IMERs) integrated into an LC-NMR system were developed for rapid and detailed structural identification of enzymatic reaction products. An on-column enzymatic reaction was achieved for immobilized cytochrome-c and dog microsomes. After the reaction, these products were analyzed by LC-NMR without any work-up processes.

Development of an automated synthesis system for preparation of glucuronides using a solid-phase extraction column loaded with microsomes.

An automated synthesis system using a solid-phase extraction (SPE) system and column packed with octadecylsilica (ODS), which was coated with phospholipid and loaded with dog liver microsomes, was developed for synthesis of glucuronides. Preparation of the microsome-immobilized SPE column, glucuronidation of drugs to synthesize the glucuronides and elution of the products were performed by an automated synthesis system. The phospholipid-coated SPE column and then the microsome-immobilized SPE column were readily prepared by allowing a solution containing L-alpha-dipalmitoylphosphatidylcholine to flow through the SPE column, and then by recycling a buffer solution containing dog liver microsomes through the resulting phospholipid-coated SPE column.

Index of the systemic balance of end products of glucocorticoid metabolism in fresh urine from humans.

Objective: Dysregulation of tissue-specific intracellular glucocorticoid reactivation is implicated in obesity and related metabolic diseases in humans. The ratio of end products of glucocorticoid metabolism in fresh urine sample, tetrahydrocortisol (THF) + allo-tetrahydrocortisol (allo-THF) vs. tetrahydrocortisone (THE), i.

Simultaneous analysis of phospholipid in rabbit bronchoalveolar lavage fluid by liquid chromatography/mass spectrometry.

A method was developed to separate and simultaneously quantitate phosphatidylglycerol (PG), phosphatidylinositol (PI), phosphatidylethanolamine (PE), phosphatidylcholine (PC), sphingomyelin (SM) and lysophosphatidylcholine (LPC) in rabbit bronchoalveolar lavage fluid (BALF) by liquid chromatography/mass spectrometry (LC/MS). This method consisted of a simple liquid-liquid extraction procedure, separation of phospholipid classes on silica gel column by gradient mode, and detection of mass spectrometry with electrospray ionization (ESI). The precision, accuracy and recovery ranged from 1.

Synthesis of acylglucuronides of drugs using immobilized dog liver microsomes octadecylsilica particles coated with phospholipid.

Immobilized dog liver microsome octadecylsilica (ODS) particles coated with phospholipid were developed for the synthesis of acylglucuronides of drugs. The phospholipid-coated ODS particles were readily prepared by stirring a solution containing L-alpha-dipalmitoylphosphatidylcholine with the ODS particles, in which the phospholipid was absorbed on the ODS surfaces by hydrophobic interaction between the acyl group of phospholipid and the otcadecyl group of the ODS particles. Similarly, the microsome-immobilized particles were readily prepared by stirring a buffer solution containing dog liver microsomes with the phospholipid-coated ODS particles, in which the microsomes were immobilized on the phospholipid-coated ODS particles by hydrophobic binding.