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Biomedical subjects

C Jurado

Publications and source records attributed to C Jurado.

11 recordsLinked to original sources

Tissue concentrations of MDMA and its metabolite MDA in three fatal cases of overdose.

The recreational use of amphetamine derivatives has become increasingly popular in our country in past recent years. Their use is especially common among young people participating in dance parties known as "raves." As a direct consequence of their increased use, the number of fatal cases in which these compounds have been involved have increased dramatically since the second half of the last decade. In our laboratory, we have registered 25 cases related to amphetamine derivatives use since 1996. Three of them were deeply studied and the results obtained are presented in this paper. This information may be useful for the interpretation of the results obtained in toxicological analysis in the cases in which death may be attributed to MDMA use.

3,4-Methylenedioxyamphetamine↗

Improved solid-phase extraction method for systematic toxicological analysis in biological fluids.

A method for the simultaneous qualitative and quantitative determination of drugs of abuse (opiates, cocaine, or amphetamines) and prescribed drugs (tricyclic antidepressants, phenotiazines, benzodiazepines, etc.) in biological fluids--blood, urine, bile, and gastric contents--was developed. This procedure involves solid-phase extraction with Bond-Elut Certify columns followed by analysis by gas chromatography-nitrogen-phosphorus detection (GC-NPD) and confirmation by gas chromatography-mass spectrometry (GC-MS), after derivatization, when necessary. Pretreatment was performed on all samples: sonication for 15 min plus enzymatic hydrolysis with beta-glucuronidase in urine. With respect to the internal standards, nalorphine and trihexylamine were used for basic substances, allobarbital for acidic drugs, and prazepam for benzodiazepines. Acidic and basic compounds were extracted from different aliquots of samples at different pH levels: 6-6.5 for the acidic and neutral and 8-8.5 for the basic and the benzodiazepines. Several areas of experimental design were considered in the process of method optimization. These included internal standards, pH, sonication, flow rate and washing solvents. It was found that systematic analysis could be reliably performed using optimized extraction conditions. The recovery rates for the compounds tested were always higher than 61.02%.

Adsorption↗

[Response to intracavernous administration of 3 different drugs in the same group of patients with erectile dysfunction].

OBJECTIVE: To compare the subjective and objective penile rigidity in the same group of patients with erectile dysfunction after intracavernous injection of different vasoactive drugs. METHODS: 91 impotent males were randomly assigned to three groups of intracavernous injection: A: 20 micrograms PGE1 B: 30 mg papaverine hydrochloride + 1 mg phentolamine (bimix), and C: 10 micrograms PGE1 + 15 mg papaverine hydrochloride + 0.5 mg phentolamine (trimix). Each patient was scheduled to receive the three modalities of intracavernous injection randomly with an interval of 7-10 days between injections. Penile rigidity equal to or more than 60% was considered positive. Subjective and objective penile rigidity were evaluated with callipers by the same observer. RESULTS: 82 patients completed the study and 9 dropped out after prolonged erection with one of the ICI modalities. Rigidity after treatment with C (66 +/- 15%) was significantly superior to that of B (59 +/- 15%, p = 0.0001) and A (60 +/- 13%, p = 0.0115). No differences were observed between A and B (p = 0.4644). Analysis of only the positive response showed significant differences between A and C, but not between C and B (p = 0.3323). Differences were not found between the response to PGE1 (A) and bimix (B) (p = 0.1275). The order of application of the drug had no effect on response (p = 0.026). CONCLUSIONS: A higher percentage of positive response in patients with erectile dysfunction was achieved with the trimix modality. Choice of more potent ICI regimens can improve the diagnostic and/or therapeutic efficacy in males that do not respond to PGE1 alone.

Adrenergic alpha-Antagonists↗

[Acceptability of auto-injection of vasoactive drugs in the treatment of erectile dysfunction].

OBJECTIVES: To study the utility of the PenInject 2.25 (SHL Medical AB), an instrument for intracavernous auto-injection of vasoactive drugs. METHODS: 61 males, aged 30-70 years, with erectile dysfunction were studied. The study comprised two groups: group A consisted of 26 patients previously treated with intracavernous injections using a syringe that were started on treatment with the self-injector, and group B consisted of 35 previously untreated patients that started treatment directly with the self-injector. Different data and questions on the facility of use and acceptance of the instrument were analyzed. Data evaluation were plotted on visual analog scales of 10 cm. A score of 5 or more showed good results and less than 5 was considered unfavorable. RESULTS: The positive aspects were facility of use, comfort, design of the self-injector, which scored higher than 7. The negative aspects were pain, fear, discomfort intensity, which scored below 4. CONCLUSIONS: The use of the PenInject self-injector in this group of patients improved the acceptability of intracavernous therapy for erectile dysfunction in comparison to the classical syringe.

Aged↗

Derivatization procedures for gas chromatographic-mass spectrometric determination of xenobiotics in biological samples, with special attention to drugs of abuse and doping agents.

The development of low cost MS detectors in recent years has promoted an important increase in the applicability of GC-MS system to analyze for the presence of foreign substances in the human body. Drugs and toxic agents are in vivo metabolized in such a way that more polar compounds are usually formed. Derivatization of these metabolites is often an unavoidable requirement for gas chromatographic analysis. Application of derivatization methods in recent years has been relevant, especially for silylation, acylation, alkylation and the formation of cyclic or diastereomeric derivatives. Given the relevance of drug of abuse testing in modern toxicology, main derivatization procedures for opiates, cocaine, cannabis, amphetamines, benzodiazepines and LSD have been reviewed. Papers describing the analyses of drugs of abuse in matrixes other than blood, such as hair or sweat, have received special attention. Advances in derivatization for sports drug testing have been particularly relevant for anabolic steroids, diuretics and corticosteroids. Among the several methodologies applied, the formation of trimethylsilyl, perfluoroacyl or methylated derivatives have proved to be both versatile and extensively used. Further advances in derivatization for GC-MS applications in clinical and forensic toxicology will depend on the one hand on the degree of further use of GC-MS for routine applications and, on the other hand, on the alternative progress made for developments in LC-MS or CE-MS. Last but not least, the appearance of comprehensive libraries in which reference spectra for different derivatives of many drugs and their metabolites are collected will have an important impact on the expansion of derivatization in GC-MS for toxicological applications.

Body Fluids↗

Time course of cocaine in rabbit hair.

The accurate interpretation of analytical results from hair testing for drugs of abuse continues to be a complex and difficult problem since many questions still remain unanswered. In this paper an animal model was developed to ascertain the time course for the appearance and disappearance of cocaine and its metabolite benzoylecgonine (BE) in hair. Female Fauve Bourgogne red-haired rabbits (n = 6) were intraperitoneally administered a single dose of cocaine at 5 mg/kg. Animal hair was shaved just before drug administration and the newly grown back hair was subsequently shaved and collected daily over a period of two weeks. Samples were analyzed for cocaine and BE by gas chromatography-mass spectrometry (GC-MS). The profiles were quite similar for parent drug and metabolite. Cocaine and BE appeared in the first sampling (day 1), with peak concentration appearing that same day. 1.01 ng/mg and 0.51 ng/mg for cocaine and BE, respectively. Levels declined rapidly on day 2, remaining detectable for ten days after drug administration. This study demonstrates that the initial incorporation of cocaine compounds in rabbit hair is very rapid (24 h). A small fraction of the drug is detected ten days after exposure, at a time when concentrations in other biological specimens (blood or urine) are not detectable.

Animals↗

Influence of the cosmetic treatment of hair on drug testing.

An important issue of concern for drug analysis in hair is the change in the drug concentration induced by the cosmetic treatment of hair. The products used for this treatment are strong bases and they are expected to cause hair damage. As a result drugs may be lost from the hair matrix or, under conditions of environmental contamination, be more easily incorporated into the hair matrix. We investigated the effects of cosmetic treatment in vivo by analysing hair samples selected from people who had treated their hair by bleaching or dyeing before sample collection. All of the subjects admitted a similar drug consumption during the time period for which the strands were analysed. Samples were viewed under a microscope to establish the degree of hair damage. Treated and untreated portions from each lock of hair were then selected, separated and analysed by standard detection procedures for cocaine, opiates, cannabinoids and nicotine. In all cases the drug content in hair that had undergone cosmetic treatment decreased in comparison to untreated hair. The majority of the mean differences were in the range of 40%-60% (cocaine, benzoylecgonine, codeine, 6-acetylmorphine and THC-COOH). For morphine the mean difference was higher than 60%, and two cases (THC and nicotine) differed by approx. 30%. These differences depended not only on the type of cosmetic treatment, as bleaching produced higher decreases than dyeing, but also on the degree of hair damage i.e. the more damaged the hair, the larger the differences in the concentration levels of drugs.

Hair↗

Simultaneous quantification of opiates, cocaine and cannabinoids in hair.

The present paper describes a sensitive method developed in our laboratory for the simultaneous analysis of opiates (morphine, codeine and monoacetylmorphine), cocainis (cocaine and benzoylecgonine) and cannabinoids (delta 9-tetrahydrocannabinol and 11-nor-delta 9-tetrahydrocannabinol-9-carboxylic acid) in hair samples. After decontaminating the sample with dichloromethane, two consecutive hydrolyses were performed in order to achieve the best conditions for extracting the three kinds of drugs from the protein matrix. First the opiate and cocainic compounds were extracted by means of a soft acidic hydrolysis with 0.1 N HCl at 50 degrees C overnight and organic solvent extraction at pH 9.2. The cannabinoids need a stronger basic hydrolysis with 11.8 N KOH for 10 min at laboratory temperature. After adding maleic acid, the cannabinoids were extracted with an organic solvent. The derivatization was carried out with heptafluorobutyric anhydride and hexafluoropropanol. Calibration curves were linear between 0.5-100 ng/mg of hair. Recovery and reproducibility were assured. The quantification limits ranged between 0.04-0.26 ng/mg of hair. Seventy hair samples from known drug abusers were cut into 1-cm segments and analyzed by this method. The ranges of measured concentrations (ng/mg) were 0.31-89 for cocaine, 0.1-5.76 for benzoylecgonine, 0.34-45.79 for morphine, 0.45-39.59 for codeine, 0.09-48.18 for monoacetylmorphine, 0.06-7.63 for THC and 0.06-3.87 for THC-COOH. The results of sectional analyses agreed with the self reported drug histories. The usefulness of this method is in assessing earlier drug consumption, and also at the same time obtaining a chronological profile of the consumption of these three types of drugs.

Cannabinoids↗

Rapid chiral separation methods development by cyclodextrin-mediated capillary electrophoresis for acidic and basic compounds.

Chiral separation methods development using conventional techniques such as GC or HPLC requires a lot of experience, effort, and expense, due to the wide diversity of the optically active solutes and their possible chiral selectors. Capillary electrophoresis has received increased attention as an alternative technique for chiral separation due to its inherent high efficiencies and ease of methods development. However, due to the wide variety of chiral selectors available in CE, the benefits of this technique might be diminished without an appropriate methods development scheme. In this paper detailed examples are shown for fast, efficient, and predictable chiral capillary electrophoresis separation methods development based on a new and systematic theory. Optimized separations and their parameters are presented for several enantiomeric acids and bases. All the three possible cases, such as the use of low and high pH, as well as pH = pK buffer systems are thoroughly discussed.

Acids↗

Hair testing for cannabis in Spain and France: is there a difference in consumption?

This paper compares the methods used in Sevilla, Spain with those used in Strasbourg, France for analyzing cannabinoids (delta 9-tetrahydrocannabinol [THC] and 11-nor-delta 9-tetrahydrocannabinol-9-carboxylic acid [THCCOOH]) in human hair. The Sevilla procedure involved the following steps: After washing the hair samples with methylene chloride at 37 degrees C for 15 min, hydrolysis was performed with 11.8N KOH (in the presence of THC-d3 and THCCOOH-d3) for 10 min at laboratory temperature, followed by the addition of maleic acid, extraction with n-hexane-ethyl acetate, and derivatization with heptafluorobutyric anhydride and hexafluoroisopropanol. Concentrations within the Spanish population ranged from 0.06 to 7.63 ng/mg and from 0.05 to 3.87 ng/mg for THC and THCCOOH, respectively. The Strasbourg procedure involved the following steps: Samples were decontaminated twice with methylene chloride, then pulverized and dissolved in 1N NaOH in the presence of THC-d3 and THCCOOH-d3. After cooling, acetic acid was added, and the samples were extracted with n-hexane-ethyl acetate, followed by a cleanup step with NaOH and HCl. Derivatization with pentafluoropropionic anhydride-pentafluoro-propanol was followed by gas chromatographic-mass spectrometric analysis using negative chemical ionization. Concentrations within the French population ranged from 0.10 to 2.17 ng/mg and from 0.05 to 0.39 ng/mg for THC and THCCOOH, respectively. In order to validate both analytical methods, 10 real hair samples from known drug abusers were analyzed by both procedures. The differences in the results ranged from 2 to 43% (mean, 25.7%) for THC and from 0 to 73.7% (mean, 36.8%) for THCCOOH. After comparing the cannabis results in hair in Spain (70 cases) and France (98 cases), we found quantitative as well as qualitative differences in cannabis consumption in the two populations.

Cannabis↗

Rapid analysis of amphetamine, methamphetamine, MDA, and MDMA in urine using solid-phase microextraction, direct on-fiber derivatization, and analysis by GC-MS.

A rapid, sensitive, and solvent-free procedure for the simultaneous determination of amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine (MDA), and 3,4-methylenedioxymethamphetamine (MDMA) in urine was developed using solid-phase microextraction (SPME) and gas chromatography-mass spectrometry (GC-MS) in the selected ion monitoring mode. A headspace vial containing the urine sample, NaOH, NaCl, and amphetamine-d3 as the internal standard was heated at 100 degrees C for 20 min. A polydimethylsiloxane fiber was maintained in the vial headspace for 10 min in order to adsorb the amphetaminic compounds, which were subsequently derivatized by exposing the fiber to trifluoroacetic anhydride for 20 min in the headspace of another vial maintained at 60 degrees C for 20 min. The trifluoroacetyl derivatives were desorbed in the GC injection port for 5 min. Several parameters were considered during the method optimization process. These included a comparison of SPME with or without headspace, the required derivatization procedure, and the influence of temperature on the headspace extraction and derivatization methods. The optimized method was validated for the four compounds tested. Calibration curves showed linearity in the range 50-1000 ng/mL (r = 0.9946-0.9999). Recovery data were 71.89-103.24%. The quantitation limits were 10 ng/mL for amphetamine and methamphetamine and 20 ng/mL for MDA and MDMA. All of these data recommend the applicability of the method for use in the analytical routine of a forensic laboratory.

3,4-Methylenedioxyamphetamine↗