Asenapine (Saphris®): GC-MS method validation and the postmortem distribution of a new atypical antipsychotic medication.

Asenapine (Saphris®) is an atypical antipsychotic approved in the USA in 2009 for the treatment of schizophrenia and bipolar disorder. The Los Angeles County Department of Coroner Toxicology Laboratory developed an analytical method for the detection and quantitation of asenapine by gas chromatography-mass spectroscopy in multiple specimens of postmortem casework. Asenapine was isolated from specimens through a basic, liquid-liquid extraction procedure and quantitated utilizing D5-fentanyl as an internal standard. Method validation for asenapine was conducted utilizing the Scientific Working Group Toxicology (SWGTOX) method validation draft proposal and the tissue distribution of four case studies was determined. The authors believe that these are the first cases to be reported in the literature and are intended to assist other forensic toxicologists with interpreting their casework.

Case study: two fatal case reports of acute yohimbine intoxication.

Yohimbine is an alkaloid that has been encountered on the streets as an aphrodisiac, hallucinogen, dietary supplement and erectile dysfunction drug. Yohimbine hydrochloride is an alpha 2-adrenoreceptor antagonist, blocking the pre- and postsynaptic alpha-2 adrenoreceptors and causing an increased release of noradrenaline and dopamine. An average oral dose of 5-15 mg produces a therapeutic whole blood level range of 40-400 ng/mL. Overdoses leading to neurotoxic effects have been seen with blood concentrations up to 5,000 ng/mL. The laboratories from the Maricopa County Medical Examiner and the Los Angeles County Department of Coroner each encountered a case in which yohimbine was identified in whole blood by means of a liquid-liquid basic drug extraction with detection on a GC-MS. Because validated quantitative methods for yohimbine did not exist at either facility, both agencies referred the blood specimens to NMS Labs, Inc. The reference laboratory analyzed the blood specimens with an LC-MS-MS and determined the quantitative values of yohimbine to be 7,400 and 5,400 ng/mL. Given the absence of other significant positive findings and the substantial yohimbine blood concentrations cited, the respective Medical Examiners determined the cause of death to be acute yohimbine intoxication with the mode being an accident. Yohimbine is a rarely encountered drug in medical examiner casework, and interpretation of the results is difficult to assess toward the cause and manner of death without such case studies being described.

Ex vivo optical coherence tomography and laser-induced fluorescence spectroscopy imaging of murine gastrointestinal tract.

Optical coherence tomography (OCT) and laser-induced fluorescence (LIF) spectroscopy each have clinical potential in identifying human gastrointestinal (GI) pathologies, yet their diagnostic capability in mouse models is unknown. In this study, we combined the 2 modalities to survey the GI tract of a variety of mouse strains and ages and to sample dysplasias and inflammatory bowel disease (IBD) of the intestines. Segments (length, 2.5 cm) of duodenum and lower colon and the entire esophagus were imaged ex-vivo with combined OCT and LIE We evaluated 30 normal mice (A/J and 10- and 21-wk-old and retired breeder C57BL/6J) and 10 mice each of 2 strains modeling colon cancer and IBD (Apc(Min) and IL2-deficient mice, respectively). Histology was used to classify tissue regions as normal, Peyer patch, dysplasia, adenoma, or IBD. Features in corresponding OCT images were analyzed. Spectra from each category were averaged and compared via Student t tests. OCT provided structural information that led to identification of the imaging characteristics of healthy mouse GI. With histology as the 'gold standard,' we developed preliminary image criteria for early disease in the form of adenomas, dysplasias, and IBD. LIF characterized the endogenous fluorescence of mouse GI tract, with spectral features corresponding to collagen, NADH, and hemoglobin. In the IBD sample, LIF emission spectra displayed potentially diagnostic peaks at 635 and 670 nm, which we attributed to increased porphyrin production by bacteria associated with IBD. OCT and LIF appear to be useful and complementary modalities for ex vivo imaging of mouse GI tissues.

Mechanistic comparison of blood undergoing laser photocoagulation at 532 and 1,064 nm.

BACKGROUND AND OBJECTIVES: We seek to compare and contrast the mechanisms of blood photocoagulation under 532 and 1,064 nm laser irradiation in vitro in order to better understand the in vivo observations. We also seek to validate a finite element model (FEM) developed to study the thermodynamics of coagulation. STUDY DESIGN/MATERIALS AND METHODS: We study the photocoagulation of whole blood in vitro at 532 and 1,064 nm using time-domain spectroscopic and optical coherence tomography (OCT)-based imaging techniques. We model the coagulation using an FEM program that includes the latent heat of vaporization (LHV) of water, consideration of the pulse shape of the laser, and the bathochromic shift in the hemoglobin absorption spectrum. RESULTS: We find significant similarities in the spectroscopic, chemical, and structural changes occurring in hemoglobin and in the blood matrix during photocoagulation despite the very large difference in the absorption coefficients. The more uniform temperature profile developed by the deeper-penetrating 1,064 nm laser allows us to resolve the structural phase transition in the red blood cells (going from biconcave disc to spherocyte) and the chemical transition creating met-hemoglobin. We find that the RBC morphology transition happens first, and that the met-Hb transition happens at a much higher temperature ( > 90 degrees C) than is found in slow bath heating. The FEM analysis with the LHV constraint and bathochromic shift predicts accurately the imaging results in both cases, and can be used to show that at 1,064 nm there is the potential for a runaway increase in absorption during the laser pulse. CONCLUSIONS: Photothermally mediated processes dominate the in vitro coagulation dynamics in both regimes despite the difference in absorption coefficients. There is a significant risk under 1,064 nm irradiation of vascular lesions in vivo that the dynamic optical properties of blood will cause runaway absorption and heating. This may in turn explain some recent results at this wavelength where full-thickness burns resulted from laser treatment.