The detection of the markers of Cannabis consumption in biological specimens is an important task for drug testing laboratories in varous contexts. A simple assay combining salting‐out assisted liquid–liquid extraction sample preparation and LC–MS/MS analysis was applied to the measurement of Δ9‐tetrahydrocannabinol, 11‐nor‐9‐carboxy‐Δ9‐tetrahydrocannabinol (THC‐COOH), 11‐hydroxy‐Δ9‐tetrahydrocannabinol, cannabinol and cannabidiol concentrations in 100 μl plasma specimens. The assay had linearity of 1–100 ng ml−1 for THC‐COOH and 0.5–50 ng ml−1 for the other tested cannabinoids. Assay validation criteria were fulfilled. Extraction yields (88.7–97.3%) and internal‐standard correct matrix effects (−9.6 to +5.4%) were acceptable. The assay was applied to 238 clinical specimens from trauma patients, with 19 samples presenting quantifiable concentrations of at least one of the target compounds. The developed assay is a simple and efficient strategy for simultaneous measurement of Δ9‐tetrahydrocannabinol, THC‐COOH, 11‐hydroxy‐Δ9‐tetrahydrocannabinol, cannabinol and cannabidiol concentrations in plasma specimens.
Background: Busulfan (BU) is an alkylating agent with a narrow therapeutic index and high intraindividual pharmacokinetic variability used in conditioning therapy for hematopoietic stem cell transplantation. Monitoring BU exposure during high-dose conditioning regimens is recommended and positively impacts outcomes. We aimed to develop, validate, and apply a ultra-high-performance liquid chromatography-mass spectrometry (MS)/MS assay to measure BU concentrations in oral fluid and dried plasma spots (DPS) as alternative matrices to plasma. Methods:We prepared plasma and oral fluid samples by protein precipitation and DPS after liquid extraction. We analyzed extracts using an LC-MS/MS system with an Acquity HSS T3 column in the positive electrospray ionization mode. The method was validated and applied to 79 paired plasma and oral fluid samples from 7 patients on BU conditioning treatment. DPS were prepared by pipetting plasma onto Whatman 903 paper. The correlation between BU in plasma, oral fluid, and DPS samples was evaluated.Results: Run time was 4.0 minutes. The assay was linear at 50-5000 ng mL 21 (r . 0.99), precise (1.9%-5.3% oral fluid and 1.8%-5.9% DPS), and accurate (98.1%-108.9% oral fluid and 93%-103.1% DPS). BU was stable in DPS at 238C for 24 hours. BU levels in oral fluid (r = 0.927) and DPS (r = 0.982) were significantly correlated with plasma. Despite the good correlation, we found a wide variation between oral fluid and plasma levels. The area under curves (AUCs) calculated with oral fluid concentrations were 79.1%-167.1% of plasma AUCs. Bland-Altman plots found a better agreement for DPS, with AUCs estimated from corrected DPS levels at 83.1%-114.1% of plasma values. Conclusions:We developed and validated a simple and fast ultrahigh-performance liquid chromatography-MS/MS assay to measure BU in oral fluid and DPS. The results do not support the use of oral fluid as a matrix for routine therapeutic drug monitoring of BU. The AUC estimated from BU measurements in DPS was comparable to that in plasma, supporting the use of DPS in BU therapeutic drug monitoring as an alternative matrix, with adequate short-term stability and logistic advantages.
Recebido em 25/8/11; aceito em 18/12/11; publicado na web em 2/3/12 FAST DETERMINATION OF BASIC DRUGS IN PLASMA BY GAS CHROMATOGRAPHY WITH NITROGEN PHOSPHORUS DETECTOR. A simple and fast method for determination of 40 basic drugs in human plasma employing gas-chromatography with nitrogen-phosphorus detection was developed and validated. Drugs were extracted from 800 µL of plasma with 250 µL of butyl acetate at basic pH. Aliquots of the organic extract were directly injected on a column with methylsilicone stationary phase. Total chromatographic run time was 25 min. All compounds were detected in concentrations ranging from therapeutic to toxic levels, with intermediate precision CV% below 11.2 and accuracy in the range of 92-114%.Keywords: GC-NPD; emergency toxicology; drug screening. INTRODUÇÃOA realização de análises toxicológicas capazes de detectar um significativo número de compostos é fundamental no contexto da toxicologia de emergência, assim como em toxicologia forense. Embora já esteja amplamente demonstrado que a identificação definitiva de uma substância requer a utilização associada de múl-tiplos métodos analíticos, 1 a cromatografia a gás (CG) empregando colunas capilares possui grande aplicabilidade na identificação e quantificação de fármacos em amostras biológicas, com diversos métodos já descritos.2-8 A elevada reprodutibilidade dos parâmetros de retenção, quando adequadamente expressos, permite a identificação de um grande número de substâncias com base em bancos de dados interlaboratoriais, especialmente no contexto da análise toxicológica sistemática (ATS), devido à disponibilidade de um banco de dados com índices de retenção de aproximadamente 4.000 substâncias. 9Entretanto, não existem publicações que descrevam a associação da abordagem qualitativa empregando este banco de dados com uma estratégia de quantificação de múltiplos analitos, especialmente considerando que a determinação quantitativa é fundamental visto que a maioria das substâncias possui efeitos tóxicos dependentes de suas concentrações plasmáticas. 10 Recentemente, diversos métodos para identificação e quantificação de múltiplos analitos em sangue, plasma ou soro em toxicologia clínica e forense foram descritos, baseados principalmente em cromatografia líquida associada à espectrometria de massas. 11-14A intenção destes métodos multianalitos é monitorar múltiplas substâncias de interesse com uma única preparação de amostra e procedimento de análise. Os métodos multianalitos em toxicologia analíticos são preferíveis porque tornam o processo analítico mais simples, rápido, barato e permitem o monitoramento de analitos de diferentes classes terapêuticas em uma única amostra corporal. Isto é relevante porque frequentemente somente uma quantidade limitada de amostra está disponível e o número total de analitos na amostra é desconhecido. Uma alternativa útil e de menor custo para a determinação de múltiplos analitos em um único método é o emprego da CG-DNP. Dentre as características vantajosas da CG para análises toxicológicas multi...
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