Detection of prohibited substances in equine hair by ultra-high performance liquid chromatography-triple quadrupole mass spectrometry - application to doping control samples.

The detection of drugs in human hair samples has been performed by laboratories around the world for many years and the matrix is popular in disciplines, such as workplace drug testing. To date, however, hair has not become a routinely utilised matrix in sports drug detection. The analysis of hair samples offers several potential advantages to doping control laboratories, not least of which are the greatly extended detection window and the ease of sample collection and storage. This article describes the development, validation, and utilisation of a sensitive ultra-high performance liquid chromatography-triple quadrupole mass spectrometry (UHPLC-MS/MS) method for the detection of 50 compounds. This provides significantly improved coverage for those analytes which would be of particular interest if detected in hair, such as anabolic steroid esters and selective androgen receptor modulators (SARMs). Qualitative validation of the method resulted in estimated limits of detection as low as 0.1 pg/mg for the majority of compounds, with all being detected at 2 pg/mg or below. The suitability of the method for the detection of prohibited substances in incurred material was demonstrated by the successful detection of several compounds, such as stanozolol, boldenone undecylenate, clenbuterol, and GW-501516, in genuine equine hair samples. Estimated concentrations of the detected substances ranged from 0.27 to 8.6 pg/mg. The method has been shown to be fit-for-purpose for routine screening of equine hair samples by the analysis of over 400 genuine hair samples.

Characterizing metabolites and potential metabolic pathways for the novel psychoactive substance methoxetamine.

The classic approach of controlled volunteer studies to study drug metabolism is difficult or impossible to undertake for novel psychoactive substances (NPS), as there is generally very limited information available to allow appropriate dose finding and safety. A viable and powerful alternative is the identification and characterization of phase I and II metabolites of such drugs by examining the concordance of data gathered from analysis of microsomal incubates with that from analysis of specimens collected from individuals with analytically confirmed use of NPS. Liquid chromatography-high resolution mass spectrometry provides the ability to reliably identify such metabolites. We used this technique here to study the metabolism of the ketamine analogue methoxetamine. A large number of metabolites were identified in the in vitro studies including normethoxetamine, O-desmethylmethoxetamine, dihydromethoxetamine, dehydromethoxetamine and several structural isomers of hydroxymethoxetamine and hydroxynormethoxetamine. pH dependent liquid-liquid extraction was used to discriminate phenolic from alcoholic metabolites. Phase II glucuronide conjugates included those of O-desmethylmethoxetamine, O-desmethylnormethoxetamine and O-desmethylhydroxymethoxetamine. The majority of these phase I and II metabolites were confirmed to be present in urine collected from three individuals presenting with acute methoxetamine toxicity.

Idiopathic retroperitoneal fibrosis. A retrospective analysis of 60 cases.

Sixty patients with idiopathic retroperitoneal fibrosis presenting between 1965 and 1984 are reviewed. Their mean age at presentation was 56 years and the male:female ratio was 3:1. The commonest presenting symptoms were flank and abdominal pain, weight loss, nausea and polyuria. Physical examination was usually normal, expect for the presence of hypertension. Anaemia and elevation of erythrocyte sedimentation rate were usually present. Proteinuria was found in less than a third of patients at presentation and significant bacteriuria was uncommon. The correct diagnosis was made or suspected in very few patients before referral. The cumulative actuarial survival rate was 86% at 1 year and 78% at 2 years. Seventeen patients died; they were significantly older and more uraemic at the time of referral than those who survived. A few patients did well with either corticosteroid therapy or ureterolysis alone. In the majority, both operation and steroid treatment were necessary. In bilateral obstruction with residual function in both kidneys, bilateral ureterolysis proved superior to unilateral operation (each followed by steroid therapy) in conserving renal function. Operation alone or steroid therapy alone should be considered in cases where steroids or surgery respectively present particular hazards. The less traumatic unilateral operation should be considered in poor risk patients and in those whose renal function is absent on one side. In many survivors, disease activity has persisted for many years. Life-long follow-up is recommended.