RESUMO
BACKGROUND: Sirolimus is indicated for prophylaxis treatment to prevent solid organ rejection. Due to intrapatient and interpatient variabilities in pharmacokinetics, risk of concentration-related toxicity, risk of noncompliance, and a high likelihood of drug-drug interactions, therapeutic drug monitoring of sirolimus is essential. There are several methodologies used clinically to monitor sirolimus, ranging from immunoassay to tandem mass spectrometry, each with potential strengths and limitations. The purpose of our study was to validate the Abbott ARCHITECT i2000 sirolimus assay. MATERIALS AND METHODS: The Abbott ARCHITECT i2000 sirolimus assay was evaluated for linearity, limit of detection, limit of quantification, imprecision, common interferences, and accuracy. Accuracy was compared with the Abbott IMx sirolimus assay and with an established liquid chromatography-tandem mass spectrometry method. Stability of sirolimus when specimens were stored frozen (-20°C) or refrigerated (2-8°C) and degree of crossreactivity of the i2000 with everolimus were also evaluated. RESULTS: The ARCHITECT i2000 assay demonstrated good linearity, low imprecision, and was free of common interferences. Results for both immunoassay methods were biased slightly high, compared with those of liquid chromatography-tandem mass spectrometry. Sirolimus was stable when samples were stored either refrigerated or frozen. However, the results generated with samples stored refrigerated had an increase in scatter on the regression plots compared with those generated for samples that were stored frozen, indicating that extraction of the drug may be incomplete, particularly with the Abbott IMx assay. In addition, statistical performance indices suggest that the agreement between the ARCHITECT i2000 and Abbott IMx was better for frozen patient samples. The ARCHITECT i2000 and the Abbott IMx methods both exhibited a >100% crossreactivity with everolimus. CONCLUSIONS: The Abbott ARCHITECT i2000 instrument demonstrates reasonable sensitivity, precision, and accuracy for supporting routine therapeutic drug monitoring of sirolimus with either refrigerated or frozen whole blood collected from patients who are not comedicated with everolimus.
Assuntos
Cromatografia Líquida/métodos , Imunossupressores/análise , Imunossupressores/sangue , Sirolimo/análise , Sirolimo/sangue , Espectrometria de Massas em Tandem/métodos , Adulto , Idoso , Monitoramento de Medicamentos/métodos , Feminino , Humanos , Imunoensaio/métodos , Masculino , Pessoa de Meia-Idade , Transplante/métodos , Adulto JovemRESUMO
CONTEXT: Synthetic cannabinoid use has increased in many states, and medicinal and/or recreational marijuana use has been legalized in some states. These changes present challenges to law enforcement drug recognition experts (DREs) who determine whether drivers are impaired by synthetic cannabinoids or marijuana, as well as to clinical toxicologists who care for patients with complications from synthetic cannabinoids and marijuana. Our goal was to compare what effects synthetic cannabinoids and marijuana had on performance and behavior, including driving impairment, by reviewing records generated by law enforcement DREs who evaluated motorists arrested for impaired driving. METHODS: Data were from a retrospective, convenience sample of de-identified arrest reports from impaired drivers suspected of using synthetic cannabinoids (n = 100) or marijuana (n = 33). Inclusion criteria were arrested drivers who admitted to using either synthetic cannabinoids or marijuana, or who possessed either synthetic cannabinoids or marijuana; who also had a DRE evaluation at the scene; and whose blood screens were negative for alcohol and other drugs. Exclusion criteria were impaired drivers arrested with other intoxicants found in their drug or alcohol blood screens. Blood samples were analyzed for 20 popular synthetic cannabinoids by using liquid chromatography-tandem mass spectrometry. Delta-9-tetrahydrocannabinol (THC) and THC-COOH were quantified by gas chromatography-mass spectrometry. Statistical significance was determined by using Fisher's exact test or Student's t-test, where appropriate, to compare the frequency of characteristics of those in the synthetic cannabinoid group versus those in the marijuana group. RESULTS: 16 synthetic cannabinoid and 25 marijuana records met selection criteria; the drivers of these records were arrested for moving violations. Median age for the synthetic cannabinoid group (n = 16, 15 males) was 20 years (IQR 19-23 years). Median age for the marijuana group (n = 25, 21 males) was 20 years (IQR 19-24 years) (p = 0.46). In the synthetic cannabinoid group, 94% (15/16) admitted to using synthetic cannabinoids. In the marijuana group, 96% (24/25) admitted to using marijuana. Blood was available for testing in 96% (24/25) of the marijuana group; 21 of these 24 had quantitative levels of THC (mean + SD = 10.7 + 5 ng/mL) and THC-COOH (mean + SD = 57.8 + 3 ng/mL). Blood was available for testing in 63% (10/16) of the synthetic cannabinoid group, with 80% (8/10) of these positive for synthetic cannabinoids. Those in the synthetic cannabinoid group were more frequently confused (7/16 [44%] vs. 0/25 [0%], p ≤ 0.003) and disoriented (5/16 [31%] vs. 0/25 [0%], p ≤ 0.003), and more frequently had incoherent, slurred speech (10/16 [63%] vs. 3/25 [12%], p = 0.0014) and horizontal gaze nystagmus (8/16 [50%] vs. 3/25 [12%], p = 0.01) than those in the marijuana group. CONCLUSION: Drivers under the influence of synthetic cannabinoids were more frequently impaired with confusion, disorientation, and incoherent, slurred speech than drivers under the influence of marijuana in this population evaluated by DREs.
Assuntos
Condução de Veículo , Canabinoides/farmacologia , Cannabis , Crime , Abuso de Maconha/psicologia , Fumar Maconha/psicologia , Extratos Vegetais/farmacologia , Psicotrópicos/farmacologia , Detecção do Abuso de Substâncias/métodos , Canabinoides/sangue , Canabinoides/síntese química , Canabinoides/isolamento & purificação , Cromatografia Líquida , Confusão/induzido quimicamente , Confusão/psicologia , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Masculino , Abuso de Maconha/sangue , Abuso de Maconha/complicações , Abuso de Maconha/diagnóstico , Fumar Maconha/efeitos adversos , Fumar Maconha/sangue , Nistagmo Patológico/induzido quimicamente , Extratos Vegetais/sangue , Extratos Vegetais/isolamento & purificação , Valor Preditivo dos Testes , Psicotrópicos/sangue , Psicotrópicos/síntese química , Psicotrópicos/isolamento & purificação , Estudos Retrospectivos , Percepção Espacial/efeitos dos fármacos , Inteligibilidade da Fala/efeitos dos fármacos , Espectrometria de Massas em Tandem , Adulto JovemRESUMO
OBJECTIVE: Evaluation of serum beta-2-microglobulin (beta2M) in an automated analyzer. DESIGN AND METHODS: The DakoCytomation beta2M kit is an antibody based reagent intended for quantitative determination of beta2M in serum and plasma by rate nephelometry. RESULTS: The limit of blank is 0.16 mg/L. The method is linear up to 17.9 mg/L. The imprecision ranged from 2.1% to 7.9% at the concentrations of 1.77 and 7.19 mg/L, respectively. Method comparison yielded slope=1.009, r=0.998. No interference was observed from hemolytic or icteric specimens. Reference interval of a healthy population was 1.13 mg/L to 3.04 mg/L. CONCLUSION: The DakoCytomation reagent is acceptable to measure serum beta2M.