RESUMEN
A boron-doped diamond electrode (BDDE) was employed for the first time in the development of a voltammetric method for the simultaneous determination of acetaminophen (ACT), caffeine (CAF) and carisoprodol (CAR). CAR presents a high oxidation potential (2.0 V) and this electrode is suitable for this purpose due to its wide electrochemical potential window. The anodic peak potentials of ACT, CAF and CAR oxidation on the BDDE were found to be 0.980 V, 1.50 V and 2.03 V (vs. Ag/AgCl (3.0 mol L-1 KCl)), respectively, by cyclic voltammetry. After optimization of the analytical conditions employing BDDE at pH 6.0 in a Britton-Robinson buffer solution, square-wave voltammetry (SWV) was applied to the simultaneous determination, by which the peak currents for the three molecules were found to vary linearly with their concentrations in the range of 2.99-283 µmol L-1 for ACT, 2.99-84.8 µmol L-1 for CAF and 19.9-207 µmol L-1 for CAR, with detection limits of 0.768 µmol L-1, 0.771 µmol L-1, and 3.11 µmol L-1, respectively. The proposed method was employed for the simultaneous determination of the three molecules in pharmaceutical formulations and the results were successfully validated with a comparative spectrophotometric method. The use of BDDE showed advantages such as low cost, suitable linearity for simultaneous quantification in real samples, no adsorption problems, and possessing rapidity and excellent reproducibility. This electrode represents a suitable electrochemical sensor for the routine analysis of these drugs.
Asunto(s)
Acetaminofén/análisis , Boro , Cafeína/análisis , Carisoprodol/análisis , Diamante , Electrodos , Reproducibilidad de los ResultadosRESUMEN
A new method of analysis has been developed for UV inactive drug carisoprodol using FTIR spectroscopy. These methods were validated for various parameters according to ICH guidelines. The proposed method has also been successfully applied for the determination of the drug concentration in a tablet formulation. The method proved to be accurate (mean percentage recovery between 95 and 105%), precise and reproducible (relative standard deviation<2%), while being simple, economical and less time consuming than other methods and can be used for routine estimation of carisoprodol in the pharmaceutical industry. The developed method also implicates its utility for other UV inactive substances. The stability of the drug under various stress conditions was studied and the drug was found to be particularly susceptible to alkaline hydrolysis. Degradation products of the alkaline hydrolysis were detected by RP-HPLC and tentatively identified by ESI-MS.
Asunto(s)
Carisoprodol/análisis , Cromatografía Líquida de Alta Presión/métodos , Relajantes Musculares Centrales/análisis , Espectroscopía Infrarroja por Transformada de Fourier/métodos , Cromatografía Líquida de Alta Presión/economía , Estabilidad de Medicamentos , Hidrólisis , Fotólisis , Reproducibilidad de los Resultados , Espectrometría de Masa por Ionización de Electrospray/economía , Espectrometría de Masa por Ionización de Electrospray/métodos , Espectroscopía Infrarroja por Transformada de Fourier/economía , Comprimidos , Rayos UltravioletaRESUMEN
The determination of carisoprodol and its metabolite meprobamate in oral fluid using solid-phase extraction and liquid chromatography with tandem mass spectral detection (LC-MS-MS) and its application to authentic specimens is described. The method employs collection of oral fluid with the Quantisal device, extraction using cation exchange/hydrophobic solid-phase columns, and LC-MS-MS in positive ion electrospray mode. The method was fully validated using various parameters, including selectivity, linearity, accuracy, intra-day and inter-day imprecision, drug recovery from the collection pad, limit of quantitation and matrix effects. The method was applied to both routine research specimens and an authentic specimen taken from an individual prescribed a daily dose of 350 mg carisoprodol following surgery.
Asunto(s)
Carisoprodol/análisis , Meprobamato/análisis , Relajantes Musculares Centrales/análisis , Saliva/química , Calibración , Carisoprodol/farmacocinética , Cromatografía Líquida de Alta Presión , Humanos , Relajantes Musculares Centrales/farmacocinética , Reproducibilidad de los Resultados , Extracción en Fase Sólida , Espectrometría de Masa por Ionización de Electrospray , Detección de Abuso de Sustancias , Espectrometría de Masas en TándemRESUMEN
A simple and reliable precolumn derivatization liquid chromatography method with ultraviolet detection has been developed and validated for the analysis of glucosamine (GS) in various dietary supplement formulations and raw materials. Additionally, the proposed method was used for analysis of carisoprodol (CR) found in ternary mixture with paracetamol (PR) and caffeine (CF). The linearity ranges were 1-100 µg/mL for GS, 1-150 µg/mL for CR, PR and CF. Derivatization was used with 1,2-naphthoquinone-4-sulphonic acid sodium salt in the presence of borate buffer. Chromatographic separation of GS-naphthoquinone derivative was achieved by using a mixture of acetonitrile and water (pH 7.3 adjusted with 0.1 M NaOH) in the ratio 10:90, v/v and flow-rate of 1.0 mL/min. UV detection was carried out at 280 nm. For PR, CF, and CR-naphthoquinone derivative, the chromatographic separation was achieved by using mixture of acetonitrile and 20 mM KH(2)PO(4) (pH 3.0 adjusted with phosphoric acid) in the ratio 20:80, v/v and flow-rate of 1.0 mL/min. UV detection was carried out at 275 nm. The limits of detection were 37.2, 35.9, 30.4 and 40.0 ng/mL for GS, CR, PR and CF, respectively.
Asunto(s)
Carisoprodol/análisis , Cromatografía Líquida de Alta Presión/métodos , Glucosamina/análisis , Acetaminofén/química , Acetonitrilos/química , Cafeína/química , Química Farmacéutica , Cromatografía de Fase Inversa , Combinación de Medicamentos , Límite de Detección , Reproducibilidad de los Resultados , Espectrofotometría Ultravioleta , Comprimidos/químicaRESUMEN
Drug-facilitated sexual assault (DFSA) is a serious and troubling crime. It is important to know if and how different drugs might be used to facilitate assault in order to deter such crime. There are a number of ways in which drugs that are used for DFSA might not be detected by routine screens. The purpose of this analysis was to draw reasonable inferences regarding drugs with a high likelihood of being used for DFSA and not being detected by routine screens. National data from poison control centres, hospital emergency rooms, and law enforcement seizures were used to evaluate the relative magnitude of problems and illicit availability associated with different classes of drugs. General drug classes were examined to include additional drugs that might be used for DFSA on the basis of their amnesic effects, widespread availability, and pharmacokinetics (i.e. short half-life). The benzodiazepine-site ligands zolpidem and eszopiclone, 'club drugs' GHB and ketamine, muscle relaxants such as carisoprodol, and antihistamines such as diphenhydramine were identified as drugs that might be used for DFSA and remain undetected by routine screens. Future studies that are designed to examine the role of these drugs in DFSA cases could provide better estimates of their use for DFSA. A better understanding of what is being missed in DFSA cases might help prioritize the development of new assays, provide rationale for the availability of particular assays for routine testing, and inform practitioners and the general public of the potential DFSA risks of certain drugs.
Asunto(s)
Violación , Detección de Abuso de Sustancias , Analgésicos/análisis , Analgésicos/farmacocinética , Analgésicos/farmacología , Animales , Benzodiazepinas/análisis , Benzodiazepinas/farmacocinética , Benzodiazepinas/farmacología , Carisoprodol/análisis , Carisoprodol/farmacocinética , Carisoprodol/farmacología , Moduladores del GABA/análisis , Moduladores del GABA/farmacocinética , Moduladores del GABA/farmacología , Alucinógenos/análisis , Alucinógenos/farmacocinética , Alucinógenos/farmacología , Antagonistas de los Receptores Histamínicos/análisis , Antagonistas de los Receptores Histamínicos/farmacocinética , Antagonistas de los Receptores Histamínicos/farmacología , Humanos , Ketamina/análisis , Ketamina/farmacocinética , Ketamina/farmacología , Relajantes Musculares Centrales/análisis , Relajantes Musculares Centrales/farmacocinética , Relajantes Musculares Centrales/farmacología , Fenciclidina/análisis , Fenciclidina/farmacocinética , Fenciclidina/farmacología , Violación/diagnóstico , Detección de Abuso de Sustancias/métodosRESUMEN
Felbamate (2-phenyl-1,3-propanediol dicarbamate) is a second generation antiepileptic drug used to treat seizures refractory to other antiepileptic drugs. With approximately 3500 new patients exposed annually, several important pharmacologic interaction questions remain unanswered necessitating the need for rapid and accurate methods of felbamate analysis in biological matrices. To this end, a rapid liquid chromatography tandem mass spectrometry (LC-MS/MS) method was developed for the measurement of felbamate in mouse plasma and tissues and human plasma. Plasma (100 µL) and tissues homogenates (100 µL of 100 mg/mL) were spiked with internal standard (carisoprodol) prior to protein precipitation with acetonitrile. Samples were chromatographed on a XBridge Phenyl, 2.5 µm, 4.6 mm×50 mm column with quantitation by internal standard reference monitoring of the ion transitions m/z 239â117 for felbamate and m/z 261â176 for carisoprodol. Calibration curves were linear from 2.5 to 500 ng/mL in mouse or human plasma and 25-5000 pg/mg in tissue homogenates. Recoveries were greater than 97% for plasma and homogenates with accuracies >92% in any of the mouse matrices and >88% in human plasma. Comparable accuracies and precision were found with and without the use of the internal standard in preparation of the calibration curves and suggest that the internal standard may not be required.
Asunto(s)
Anticonvulsivantes/análisis , Cromatografía Liquida/métodos , Fenilcarbamatos/análisis , Glicoles de Propileno/análisis , Espectrometría de Masas en Tándem/métodos , Animales , Anticonvulsivantes/sangre , Anticonvulsivantes/química , Química Encefálica , Carisoprodol/análisis , Carisoprodol/química , Felbamato , Humanos , Análisis de los Mínimos Cuadrados , Hígado/química , Ratones , Fenilcarbamatos/sangre , Fenilcarbamatos/química , Glicoles de Propileno/sangre , Glicoles de Propileno/química , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
Facilities involved in the manufacture of pharmaceutical products are an under-investigated source of pharmaceuticals to the environment. Between 2004 and 2009, 35 to 38 effluent samples were collected from each of three wastewater treatment plants (WWTPs) in New York and analyzed for seven pharmaceuticals including opioids and muscle relaxants. Two WWTPs (NY2 and NY3) receive substantial flows (>20% of plant flow) from pharmaceutical formulation facilities (PFF) and one (NY1) receives no PFF flow. Samples of effluents from 23 WWTPs across the United States were analyzed once for these pharmaceuticals as part of a national survey. Maximum pharmaceutical effluent concentrations for the national survey and NY1 effluent samples were generally <1 microg/L. Four pharmaceuticals (methadone, oxycodone, butalbital, and metaxalone) in samples of NY3 effluent had median concentrations ranging from 3.4 to >400 microg/L. Maximum concentrations of oxycodone (1700 microg/L) and metaxalone (3800 microg/L) in samples from NY3 effluent exceeded 1000 microg/L. Three pharmaceuticals (butalbital, carisoprodol, and oxycodone) in samples of NY2 effluent had median concentrations ranging from 2 to 11 microg/L. These findings suggest that current manufacturing practices at these PFFs can result in pharmaceuticals concentrations from 10 to 1000 times higher than those typically found in WWTP effluents.
Asunto(s)
Analgésicos Opioides/química , Residuos de Medicamentos/análisis , Monitoreo del Ambiente/métodos , Preparaciones Farmacéuticas/análisis , Contaminantes Químicos del Agua/análisis , Purificación del Agua/métodos , Barbitúricos/análisis , Carisoprodol/análisis , Metadona/análisis , Relajantes Musculares Centrales/análisis , Oxazolidinonas/análisis , Oxicodona/análisis , Estados UnidosRESUMEN
Gamma-hydroxybutyrate (GHB) is best known as a recreational depressant drug, whose use has also been implicated in drug facilitated sexual assault cases. It is also available as a therapeutic agent (Xyrem) used for the treatment of daytime sleepiness or cataplexy associated with narcolepsy. This is a report of a case of a 53-year-old woman undergoing treatment with Xyrem for narcolepsy. The decedent was also prescribed tramadol, gabapentin, cetirizine, modafinil, carisoprodol, and Xyrem. Toxicological analysis of the blood revealed GHB 165.6 mg/L, and 90.7 mg/L in the urine. Blood GHB concentrations in the range 156-260 mg/L have been reported to induce moderately sound sleep. The combined use of central nervous system depressant drugs, together with her problematic sleep apnea, and snoring (both contraindications for GHB use) were determined to have caused this subject's death. The manner of death was determined to be accidental.
Asunto(s)
Depresores del Sistema Nervioso Central/envenenamiento , Narcolepsia/tratamiento farmacológico , Oxibato de Sodio/envenenamiento , Aminas/análisis , Aminas/envenenamiento , Compuestos de Bencidrilo/análisis , Compuestos de Bencidrilo/envenenamiento , Carisoprodol/análisis , Carisoprodol/envenenamiento , Depresores del Sistema Nervioso Central/análisis , Cetirizina/análisis , Cetirizina/envenenamiento , Ácidos Ciclohexanocarboxílicos/análisis , Ácidos Ciclohexanocarboxílicos/envenenamiento , Interacciones Farmacológicas , Quimioterapia Combinada , Femenino , Toxicología Forense , Gabapentina , Contenido Digestivo/química , Humanos , Persona de Mediana Edad , Modafinilo , Síndromes de la Apnea del Sueño/complicaciones , Ronquido/complicaciones , Oxibato de Sodio/análisis , Tramadol/efectos adversos , Tramadol/análisis , Cuerpo Vítreo/química , Ácido gamma-Aminobutírico/análisis , Ácido gamma-Aminobutírico/envenenamientoRESUMEN
This article discusses the immunoassay screening of pain management drugs, and the mass spectrometric confirmation of fentanyl in human hair. Hair specimens were screened for fentanyl, opiates (including oxycodone), tramadol, propoxyphene, carisoprodol, methadone, and benzodiazepines and any positive results were confirmed using gas chromatography or liquid chromatography with mass spectral detection. The specific focus of the work was the determination of fentanyl in hair, since autopsy specimens were also available for comparison with hair concentrations. Using two-dimensional gas chromatography with electron impact mass spectrometric detection, fentanyl was confirmed in four of nine hair specimens collected at autopsy. The accuracy of the assay at 10 pg/mg was 95.17% and the inter-day and intra-day precision was 5.04 and 13.24%, respectively (n=5). The assay was linear over the range 5-200 pg/mg with a correlation of r(2)>0.99. The equation of the calibration curve forced through the origin was y=0.0053x and the limit of quantitation of the assay was 5 pg/mg. The fentanyl concentrations detected were 12, 17, 490, and 1930 pg/mg and the results were compared with toxicology from routine post-mortem analysis. The screening of pain management drugs in hair is useful in cases where other matrices may not be available, and in routine testing of hair for abused drugs.
Asunto(s)
Analgésicos Opioides/análisis , Fentanilo/análisis , Cabello/química , Benzodiazepinas/análisis , Carisoprodol/análisis , Dextropropoxifeno/análisis , Ensayo de Inmunoadsorción Enzimática , Toxicología Forense , Cromatografía de Gases y Espectrometría de Masas , Humanos , Metadona/análisis , Oxicodona/análisis , Detección de Abuso de Sustancias , Tramadol/análisisRESUMEN
Carisoprodol is commonly prescribed as a centrally acting muscle relaxant, but it is also subject to abuse. The literature describing fatal intoxications with the drug is limited to a relatively small number of cases, and there are inconsistencies with regard to which concentration levels that are toxic. We therefore investigated all forensic autopsies at the Norwegian Institute of Public Health during the period 1992-2003 where carisoprodol was detected. The median concentrations of carisoprodol in intoxication with carisoprodol only or with only minor other analytical findings was 36 mg/l (range 8-65 mg/l; n=5). In the rest of the intoxications, the relevance of carisoprodol relative to the other drugs detected was variable (n=93). When the number of intoxications with carisoprodol each year were divided by the number of defined daily doses (DDD) sold, a fatal toxicity index between 5.6 and 6.9 deaths/1 million DDD was obtained. The total number of cases where carisoprodol was detected increased during the period studied, which correlated to sales figures for the drug. We conclude that carisoprodol can be fatal in concentrations below those indicated in some of the previously published literature. There were, however, only a small number of cases where the cause of death can be attributed to use of carisoprodol alone.
Asunto(s)
Carisoprodol/envenenamiento , Relajantes Musculares Centrales/envenenamiento , Adolescente , Adulto , Anciano , Carisoprodol/análisis , Prescripciones de Medicamentos/estadística & datos numéricos , Femenino , Toxicología Forense , Humanos , Masculino , Meprobamato/análisis , Meprobamato/envenenamiento , Persona de Mediana Edad , Relajantes Musculares Centrales/análisis , Intoxicación/mortalidad , Estudios Retrospectivos , Detección de Abuso de Sustancias , SuicidioRESUMEN
Carisoprodol (CSP) is a musculoskeletal relaxant whose active metabolite is meprobamate (MPB). This drug has recently been noticed to be abused as an inexpensive alternative to illicit drugs in Korea. A method using solid-phase extraction (SPE) and gas chromatography/mass spectrometry (GC/MS) was developed for the determination of CSP and MPB in human hair. Hair samples (30 mg) were washed with distilled water and acetone, cut into small fragments (<1 mm), incubated in 1.0 M HCl overnight at 50 degrees C, and then adjusted to pH 6.5. The drugs were extracted from the resulting hydrolyzed solutions using a SPE column. The eluents were evaporated to dryness, then derivatized using N,O-bis(trimethylsilyl)trifluoroacetamide (BSTFA) with 1% trimethylchlorosilane (TMCS) at 120 degrees C for 30 min. The derivatized extract (1 microL) was injected into the GC/MS system. Recoveries were in the range of 91.5-93.1% for CSP and 85.5-93.0% for MPB. The linear ranges were 0.5-10.0 ng/mg for both CSP and MPB with good correlation coefficients (r(2) = 0.995). The intra-day precision and accuracy ranged from 1.5 to 9.3% and -17.5 to 3.6%, respectively, and the inter-day precision and accuracy ranged from 3.9 to 6.2% and -15.0 to -3.9%, respectively. The limits of detection for CSP and MPB were 0.13 and 0.12 ng/mg, respectively. The applicability of the method was proven by analyzing a hair sample from an authentic abuser.
Asunto(s)
Carisoprodol/análisis , Cromatografía de Gases y Espectrometría de Masas/métodos , Cabello/química , Meprobamato/análisis , Relajantes Musculares Centrales/análisis , Detección de Abuso de Sustancias/métodos , Adulto , Carisoprodol/química , Humanos , Masculino , Meprobamato/química , Relajantes Musculares Centrales/química , Compuestos de Trimetilsililo/químicaRESUMEN
Drug testing plays an important role in the provision of information to health authorities on trends in drug abuse. In the Republic of Korea, the testing of urine and postmortem specimens has been used as part of a programme to monitor and control the abuse of non-controlled drugs, i.e., substances that were not originally included in the lists of controlled substances in that country. Zipeprol, dextromethorphan, carisoprodol and nalbuphine are examples of such drugs, which are widely used as medicines. Increasing levels of abuse of these drugs, including abuse that resulted in fatalities, were confirmed in the Republic of Korea by the results of drug testing. Based on the accumulated data from postmortem specimens, the health authorities in the Republic of Korea subsequently introduced controls on these drugs. A significant drop in fatalities related to the abuse of these non-controlled drugs underlined the importance of timely action for improving community health. In the context of drug testing, the analysis of non-controlled and new drugs always presents a scientific challenge, because specific analytical methods for testing for those drugs are not available. In the Republic of Korea, as part of the drug abuse warning programme, it was necessary to establish methods for the detection and quantification in biological fluids of all four non-controlled drugs and their metabolites in order to monitor the trends in drug abuse. The present paper puts forward epidemiological and clinical data on abuse and fatalities associated with zipeprol, dextromethorphan, carisoprodol and nalbuphine, as well as details of the analytical methods developed.
Asunto(s)
Control de Medicamentos y Narcóticos/legislación & jurisprudencia , Drogas Ilícitas/análisis , Medicamentos bajo Prescripción/análisis , Detección de Abuso de Sustancias/legislación & jurisprudencia , Trastornos Relacionados con Sustancias/diagnóstico , Trastornos Relacionados con Sustancias/mortalidad , Adolescente , Adulto , Autopsia/legislación & jurisprudencia , Líquidos Corporales/química , Carisoprodol/análisis , Carisoprodol/envenenamiento , Niño , Comparación Transcultural , Dextrometorfano/análisis , Dextrometorfano/envenenamiento , Interacciones Farmacológicas , Sobredosis de Droga/mortalidad , Femenino , Humanos , Drogas Ilícitas/envenenamiento , Corea (Geográfico) , Masculino , Persona de Mediana Edad , Nalbufina/análisis , Nalbufina/envenenamiento , Piperazinas/análisis , Piperazinas/envenenamiento , Vigilancia de la Población , Medicamentos bajo Prescripción/envenenamiento , Detección de Abuso de Sustancias/métodos , Suicidio/legislación & jurisprudencia , Adulto JovenAsunto(s)
Carisoprodol/envenenamiento , Sobredosis de Droga/etiología , Relajantes Musculares Centrales/envenenamiento , Adulto , Antídotos/uso terapéutico , Carisoprodol/análisis , Carbón Orgánico/administración & dosificación , Clordiazepóxido/envenenamiento , Clindamicina/uso terapéutico , Sobredosis de Droga/patología , Sobredosis de Droga/terapia , Quimioterapia Combinada , Flumazenil/uso terapéutico , Lavado Gástrico , Humanos , Masculino , Relajantes Musculares Centrales/análisis , Naloxona/uso terapéutico , Bicarbonato de Sodio/uso terapéutico , Sorbitol/administración & dosificación , Temazepam/envenenamiento , Resultado del TratamientoRESUMEN
During a 6-month monitoring period, carisoprodol was detected in the urine specimens of 19 patients for whom drug screening had been ordered for purposes of patient care. The clinical history suggested that in 7 cases the drug was abused or implicated in a suicide attempt or gesture. In another 7 cases, the drug was used primarily for medical purposes, and in 5 cases the reason for use could not be determined. One patient ingested homemade tablets that were found to contain carisoprodol. In an additional case, the drug was detected in breast milk. Physical findings, clinical history, and treatment are described, and the profile of a typical carisoprodol user is discussed. It seems that carisoprodol has become an unrecognized drug of abuse, at least in our community. This drug and its metabolite, meprobamate, should be included in comprehensive drug screening.
Asunto(s)
Carisoprodol/orina , Detección de Abuso de Sustancias , Adolescente , Adulto , Carisoprodol/análisis , Femenino , Humanos , Drogas Ilícitas , Masculino , Meprobamato/orina , Persona de Mediana Edad , Leche Humana/química , Intento de Suicidio , ComprimidosRESUMEN
Three cases involving overdoses of carisoprodol are presented. Concentrations of carisoprodol and its major metabolite meprobamate, were determined in urine, vitreous humor, heart, and femoral blood. All drugs were quantified by gas chromatography/mass spectrometry (GC/MS).
Asunto(s)
Carisoprodol/farmacocinética , Adulto , Carisoprodol/análisis , Carisoprodol/envenenamiento , Femenino , Cromatografía de Gases y Espectrometría de Masas , Humanos , Indicadores y Reactivos , Masculino , Meprobamato/análisis , Meprobamato/sangre , Meprobamato/orina , SuicidioRESUMEN
A method for the identification and quantification of meprobamate or carisoprodol in plasma by GC/FID is presented. The method employs vinylbarbital as the internal standard and requires no derivatization. After a single extraction, analysis is achieved in 7 min. This method is thus rapid, sensitive, reproducible, selective, and applicable to forensic and clinical toxicological analyses.