Derivatization of (5R)-hydroxytriptolide from benzylamine to enhance mass spectrometric detection: application to a Phase I pharmacokinetic study in humans.

(5R)-Hydroxytriptolide, a semisynthetic structural analog of triptolide, exhibits anti-inflammatory and immunosuppressive effect both in vitro and in vivo. The compound is currently undergoing Phase I clinical trials. This work describes the quantification of (5R)-hydroxytriptolide in human plasma based on chemical derivatization from benzylamine. Analysis through liquid chromatography-tandem mass spectrometry (LC-MS/MS) is performed for characterization. The primary reaction product between (5R)-hydroxytriptolide and benzylamine was identified as a 12,13-epoxide ring adduct. For quantification in plasma, (5R)-hydroxytriptolide and the internal standard (triptolide) were first extracted from diethyl ether-dichloromethane (3:2, v/v) and then converted to their benzylamine derivates at 80°C for 1 h. The analytes are separated on a Gemini 5 µm 100 Å column, using a gradient elution program with a solvent consisting of 0.77 mM ammonium hydroxide (pH 10.0) and acetonitrile. An API 4000 tandem mass spectrometer operated in positive ion mode and equipped with an electrospray ionization source is used as detector. This method allows for a lower limit of quantification of 0.030 ng mL(-1). The validation results show accuracy (%RE<11.7) and precision (%RSD<8.6) at a broad linear dynamic range (0.030-100 ng mL(-1)). The simple and quantitative derivatization coupled with tandem mass spectrometric analysis yields a sensitive and robust method for the quantification of (5R)-hydroxytriptolide in Phase I pharmacokinetic studies.

Technical analysis of dual channel pulse generators used in deep brain stimulation; a safety evaluation.

BACKGROUND: A sudden failure of implantable pulse generators (IPG) occurred in 15 out of 143 units during the last 4 years in our patients. This corresponds to a failure rate of 10.5%. In all cases, the connection between the causes of battery and electronic circuit was found defective in the destructive analysis. In order to better understand the failure causes we proceeded to an analysis of explanted IPGs which had reached their normal life span due to depletion of the battery. METHOD: A functional test and an intensive destructive analysis were carried out in 14 units. The internal parts of the IPG were inspected by light and electron microscopy. FINDINGS: Deformations of the connection between battery and electronic circuit could be found in 12 out of 14 IPGs. The epoxy bonds, which achieve the mechanical fixation between the two contact areas of the bond wires, were found separated in 86%. Additionally, in six out of 14 devices the bond wires were either found lifted or with cracks as a sign of material fatigue. CONCLUSION: Based on these results we conclude that the IPGs of the affected series did have a technical weak spot. We presume that this issue appears systematically and not randomly or triggered by an unusual action of the patient.

Complete assignments of (1)H and (13)C NMR data for two 3beta,8beta-epoxymexicanolides from the fruit of a Chinese mangrove Xylocarpus granatum.

Three 3beta,8beta-epoxymexicanolides, including xyloccensin K, 6-acetoxycedrodorin and a new one named xyloccensin W, were isolated from the fruit of a Chinese mangrove Xylocarpus granatum. Their structures were determined by spectroscopic analyses. The first complete assignment of (1)H and (13)C NMR data for xyloccensin W was achieved by means of 2D NMR techniques, including (1)H-(1)H COSY, HSQC, HMBC and NOESY spectra. In addition, the confusion of (1)H and (13)C NMR data previously reported for xyloccensin K was clarified.

Epoxy putty for free-form external skeletal fixators.

OBJECTIVE: To evaluate the suitability of epoxy putty for use as a connecting beam material in a free-form external skeletal fixator. DESIGN: Mechanical evaluation of beams and the pin-material interface of commonly used methacrylates and the proposed epoxy putty. PROCEDURE: The apparent modulus, bending strength, and toughness of 10 beams of three methacrylates (Technovit, APEF System, Bone Cement) and three epoxy putties (Oatey Epoxy Putty, All-Metals PowerPoxy, and Plumber's PowerPoxy) were determined in three-point bending. The shear strength of smooth and roughened-shaft pins embedded in the three methacrylates and the Oatey Epoxy Putty was determined by pull-out testing. RESULTS: The epoxy putties had similar strength, greater apparent modulus, and reduced toughness when compared with the methacrylates. The shear strength of the smooth pin interface with the Oatey Epoxy putty was greater than that with the methacrylates. The interface with roughened pins was much stronger than that with smooth pins for all materials tested. CLINICAL RELEVANCE: Epoxy putty is a suitable material for free-form external fixators. It is easy to handle, inexpensive, and has suitable setting times and mechanical properties.