Thermodynamic signatures of quantum criticality in cuprate superconductors.

The three central phenomena of cuprate (copper oxide) superconductors are linked by a common doping level p*-at which the enigmatic pseudogap phase ends and the resistivity exhibits an anomalous linear dependence on temperature, and around which the superconducting phase forms a dome-shaped area in the phase diagram1. However, the fundamental nature of p* remains unclear, in particular regarding whether it marks a true quantum phase transition. Here we measure the specific heat C of the cuprates Eu-LSCO and Nd-LSCO at low temperature in magnetic fields large enough to suppress superconductivity, over a wide doping range2 that includes p*. As a function of doping, we find that Cel/T is strongly peaked at p* (where Cel is the electronic contribution to C) and exhibits a log(1/T) dependence as temperature T tends to zero. These are the classic thermodynamic signatures of a quantum critical point3-5, as observed in heavy-fermion6 and iron-based7 superconductors at the point where their antiferromagnetic phase comes to an end. We conclude that the pseudogap phase of cuprates ends at a quantum critical point, the associated fluctuations of which are probably involved in d-wave pairing and the anomalous scattering of charge carriers.

[Feasibility of a psychoeducation group for patients with anorexia nervosa: An open study]. / Faisabilité d'un groupe de psychoéducation dans l'anorexie : une étude ouverte.

INTRODUCTION: Management of anorexia nervosa is difficult and few treatments have shown their effectiveness, justifying the exploration of new therapeutic approaches. Available evidence suggests an interest of psychoeducational groups in a significant number of psychiatric disorders. In patients suffering from anorexia, to date there are few groups or interventions available. We aimed to assess the feasibility and acceptability of a psycho-educational program promoting information about the disease and presenting techniques that can help to cope with anorexia and the functional impact it causes. The exploratory secondary objectives were to evaluate if such a group is associated with clinical improvement. METHOD: Twenty-seven patients suffering from anorexia nervosa, in three groups, received eight weekly interventions in addition to their usual care. The study was open-label and non-randomized. Patients were assessed three times (baseline, at the end of the group and three months later). The assessments were both qualitative (Eating Disorder Examination questionnaire, The Anorexia Nervosa Stage of Change Questionnaire, the Eating Disorders Quality of Life questionnaire, Work and Social Adjustment Scale) and qualitative. RESULTS: Seventy-eight percent of participants attended more than 75 % of the sessions. Seventy percent of participants found the group useful, and 95 % said it helped them improve their knowledge of the disease and its consequences. The average BMI of participants changed significantly with an average increase of 2.5kg between baseline and the three month assessment. There was an improvement of the eating disorders features in EDE-Q for the total score and for all subscores. The improvement in the total score was significant at the end of the group sessions, while the improvement in the sub scores became significant at three months. There was also a significant mood improvement at the end of the group. Finally, there was a significant improvement in daily functioning with a decrease in Work and Social Adjustment Scale scores and an improvement in quality of life. On qualitative assessment, patients were satisfied with the care proposal. They were able to appreciate the support and sharing of experience provided by the group formula. Most of them reported changes in their daily lives, either in their relationship to care and illness, or in their relationships with their loved ones, their leisure/work, their mood or their eating behavior. CONCLUSION: Both qualitative and quantitative results suggest that this group psychoeducation program is feasible and well accepted by patients in addition to usual management. Although the methodology does not allow any conclusions, the clinical improvements observed during the group are encouraging with regard to the safety of this type of intervention and its possible effectiveness and argue for a controlled study.

The impulsiveness level influences the salivary cortisol response and social stress sensitivity in suicidal patients.

INTRODUCTION: Suicide attempters (SA) are more vulnerable to social stress and show disturbed cortisol response in stressful conditions compared with psychiatric and healthy controls. Recent data suggest that this dysregulation might be related to impulsivity traits. However, little is known about the emotional consequences of social stress in SA exposed to stress. OBJECTIVES: The aim of our study was to evaluate the cortisol and emotional responses to social stress in patients with depression with and without suicide attempt, by taking into account impulsivity traits and depression severity. METHODS: 67 adult women (41 SA and 26 affective controls (AC,i.e. without suicide attempt history)) with lifetime history of major depressive episode were included. Patients performed the Trier Social Stress Test (TSST), a well-validated social stress task. Patients provided seven saliva samples, to measure the cortisol response, and filled in questionnaires to assess psychological pain, positive and negative mood, and anxiety at different time points (from 10 min before to 120 min after the TSST). Moderated regression models were used including suicide attempt history, depression severity, and impulsivity as independent variables and their interactions. RESULTS: In patients with low depression and high impulsivity, salivary cortisol response during the TSST was higher in SA than in AC (p < .001). Psychological pain, negative mood, and anxiety were increased in all patients just after the TSST, followed by a decrease at 120 min. Positive mood recovery was slower in SA, and in patients with high impulsivity and low depression level (p < .001). CONCLUSIONS: Impulsivity traits have an important role in suicidal vulnerability in stress conditions. Impulsivity traits might help to differentiate patients at risk of suicide who are highly sensitive to stress when depression level is low. Higher impulsiveness may increase the sensitivity to emotional distress that translates into inadequate physiological responses.

Spontaneous prolactin transplantable tumor in the Wistar/Furth rat (SMtTW): a new animal model of human prolactinoma.

Two spontaneous prolactinomas, removed from 28-mo-old female Wistar/Furth rats, were grafted by serial passages under the kidney capsule and the skin in 117 females of the same consanguineous strain. The hosts, aged between 2 and 10 mo, were free of estrogen treatment. These transplantable tumors, named SMtTW1 and SMtTW2, were studied until the fifth serial passage. The percentage of success was 100% under the kidney capsule and 20% under the skin. From the radioimmunoassays of prolactin (PRL), growth hormone, and adrenocorticotropic hormone and the immunocytochemical results, the tumors secrete PRL only. The PRL tumoral secretion was detected after 3 to 5 mo of graft; at 8 mo, mean plasma PRL values reached 5150 ng/ml (normal value, 15.2 ng/ml). Plasma growth hormone and adrenocorticotropic hormone values remained normal. Like the primary tumors, the grafted tumors were benign, grew slowly, and were sparsely granulated well-differentiated prolactinomas with exocytosis. They remained identical during the first serial passages. The secretion and the growth of SMtTW2 were inhibited by bromocriptine. In the light of our knowledge of the human prolactinoma, the spontaneous transplantable prolactinoma of the rat may be considered to be an animal model closer to the human pathology than the estrogen-induced "tumors" and the induced transplantable tumors. It is easier to use than the spontaneous prolactinoma of the rat.

Morphofunctional modifications associated with the inhibition by estradiol of MtTF4 rat pituitary tumor growth.

The MtTF4 pituitary tumor has been induced in Fischer rats by chronic estrogen administration. Recently, we reported that sustained pharmacological treatment of Fischer rats with 17 beta-estradiol inhibited the growth of the MtTF4 tumor transplanted s.c. The present work describes the associated morphofunctional changes occurring in the tumor during 17 beta-estradiol inhibition. It is shown that a 7-day 17 beta-estradiol treatment resulted in an increase of the surface area of cells, nuclei, nucleoli, Golgi complexes, and rough endoplasmic reticulum and an increase in the number of euchromatin-rich nuclei. Flow cytometry analysis of DNA distribution suggested that estradiol affects the cell progression through the early S phase. The ratio of RNA to DNA increased significantly, reflecting cell hypertrophy. Moreover, there was a significant increase in tumor prolactin concentration and a marked enhancement in the intensity of the immunocyto-chemical reaction with rat prolactin antiserum. On the other hand, cell mitoses were dramatically decreased. These morphofunctional changes indicate that the inhibition of the tumor growth by estradiol is accompanied by an evolution of the tumor cell population towards a more differentiated state. However, it cannot be decided whether 17 beta-estradiol induces a shift from a proliferative state to a differentiated state or whether 17 beta-estradiol treatment results in a selection of a subpopulation of tumor cells that are slow growing and more differentiated.

Effects of aluminum on bone surface ion composition.

Aluminum induces net calcium efflux from cultured bone. To determine whether aluminum alters the bone surface ion composition in a manner consistent with predominantly cell-mediated resorption, a combination of cell-mediated resorption and physicochemical dissolution or physicochemical dissolution alone, we utilized an analytic high-resolution scanning ion microprobe with secondary ion mass spectroscopy to determine the effects of aluminum on bone surface ion composition. We cultured neonatal mouse calvariae with or without aluminum (10(-7) M) for 24 h and determined the relative ion concentrations of 23Na, 27Al, 39K, and 40Ca on the bone surface and eroded subsurface. Control calvariae have a surface (depth approximately 6 nm) that is rich in Na and K compared with Ca(Na/Ca) = 24.4 + 1.4, mean + 95% confidence limit of counts per second of detected secondary ions, K+Ca = 13.2 + 0.9). Aluminum is incorporated into the bone and causes a depletion of surface Na and K relative to Ca (Na/Ca = 9.6 + 0.7, K/Ca = 4.9 + 0.4; each p < 0.001 versus control). After erosion (depth approximately 50 nm), control calvariae have more Na and K than Ca (Na/Ca = 16.0 + 0.1, K/Ca = 7.5 + 0.1); aluminum again depleted Na and K relative to Ca (Na/Ca = 4.1 + 0.1 K/Ca = 1.9 + 0.1; each p < 0.001 versus control). Aluminum produced a greater net efflux of Ca (362 +/- 53, mean +/- SE, nmol/bone/24 h) than control (60 +/- 30, p < 0.001). With aluminum, the fall in the ratios of both Na/Ca and K/Ca coupled with net Ca release from bone indicates that aluminium induces a greater efflux of Na and K than Ca from the bone surface and is consistent with an aluminum-induced removal of the bone surface. This alteration in surface ion concentration and calcium efflux is consistent with that observed when calcium is lost from bone through a combination of cell-mediated resorption and physicochemical dissolution.

Inhibitory effects of the dopamine agonists quinagolide (CV 205-502) and bromocriptine on prolactin secretion and growth of SMtTW pituitary tumors in the rat.

The SMtTW tumor, a spontaneous PRL-secreting transplantable tumor, is the only available animal model sensitive to dopamine agonists. This model has been used to compare the long term in vivo effects of CV 205-502 (CV) and bromocriptine (BR) on PRL secretion and tumor growth. These two drugs were given for 2 months to female Wistar-Furth rats bearing either small or large tumors 4 and 6 months after the graft. Untreated grafted rats served as control. In all rats treated with 5 or 10 mg/kg.day BR or 0.3 mg/kg.day CV, a normalization of plasma PRL levels was observed whatever the pretreatment levels (plasma PRL or CV or BR-treated rats, < 15 ng/ml vs. 28253 ng/ml in control rats 8 months after graft). An inhibition of tumor growth was found for both small and large tumors, but the tumors never disappeared completely (mean tumor weights at autopsy, 440 and 660 mg in BR and CV groups vs. 5270 mg in control group 8 months after graft). Experiments performed with increasing doses of BR (0.15-5 mg/kg.day) or CV (0.03-0.6 mg/kg.day) indicated that CV is effective at doses 5-10 times lower than those of BR. A shrinkage under treatment and a regrowth after drug withdrawal were demonstrated for large tumors by in vivo ultrasonographic measurements of tumor size. Histological and ultrastructural effects were similar for the two drugs: decrease in hemorrhage, reduction of the cell size and secretory activity, increase in immunoreactive PRL cellular content, and inhibition of exocytosis. There was no difference in the PRL mRNA content of treated and untreated tumors, as assessed by in situ hybridization. In conclusion, CV and BR exhibit similar inhibitory effects on tumor growth and PRL secretion. These effects are rapidly and fully reversible after drug withdrawal. The present results give a complete account of the actions of the two dopamine agonists under conditions comparable to those used in the treatment of human prolactinomas.

Somatotropic adenoma manifested by galactorrhea without acromegaly.

In two of eight premenopausal women with somatotropic adenomas, galactorrhea was the earliest clinical feature, associated in one patient with amenorrhea. These two patients did not have clinically evident acromegaly. Mean basal serum GH levels were elevated and did not decrease after glucose ingestion. Both patients had modest hyperprolactinemia. Histological and immunocytological studies of the adenomas showed numerous adenomatous somatotropic cells and some alpha-subunit- and PRL-containing cells. In these patients, the origin of the hyperprolactinemia was not clear. In one patient, elevated GH secretion was probably responsible for the galactorrhea, since it disappeared after surgical treatment despite persistence of hyperprolactinemia. In conclusion, galactorrhea, isolated or associated with amenorrhea, can be the only clinical manifestation of a somatotropic adenoma.

A human beta-endorphin pituitary adenoma.

A beta-endorphin (beta END)-containing pituitary adenoma was demonstrated by immunocytochemical, biochemical, and ultrastructural methods in a 43-yr-old man who had impotence, slight testicular atrophy, and an enlarged sella turcica (grade II0), but no manifestations of Cushing's disease. Preoperative hormone data revealed hyperprolactinemia (97 ng/ml), low plasma cortisol levels without circadian rhythm, undetectable plasma ACTH, and normal plasma FSH and LH levels, with an impaired response to LRH. After hypophysectomy, these hormone levels normalized and responded normally to dynamic tests. Immunocytochemically, 30% of the tumor cells reacted only with beta END antiserum. beta END immunoreactivity was the only component revealed by RIA and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. A characteristic ultrastructural aspect is also described. These findings demonstrate dissociation in the secretion of the proopiomelanocortin-derived peptides and suggest a relationship between hyperprolactinemia and tumor secretion of beta END.

Mapping of corticotropic cells in the normal human pituitary.

We accomplished the first mapping of corticotropic cells in the whole human adult pituitary. Corticotropic cells were identified by immunocytochemistry (ICC) and quantified by image analysis on 12 pituitaries obtained from people who had died suddenly. An overall view of each pituitary was given by 15-21 sections (mean 18 sections) at 300-micron intervals on six slides. Each section was systematically treated by indirect immunoperoxidase using an anti-ACTH[17-39] polyclonal antiserum. All the measures were done with a x 6.3 objective lens, each field (0. 5 mm2) being considered as the unit area. The mean pituitary density (surface of labeled cells/total surface) of corticotropic cells (9.5 +/- 3.0% per 0. 5 mm2) is significantly higher in men (11.5 +/- 5.1%) than in women (7.0 +/- 1.3%). This difference is due to an inverse relationship between the corticotropic cell density and the weight of the pituitary, which is higher in women than in men. The mean diameter of corticotropic cells is 14.9 micron and their total number per pituitary is approximately 10(7) cells. We confirmed that the spatial distribution of corticotropic cells is nonuniform: they are mainly distributed in the anteromedian part of the anterior lobe. In addition, our results demonstrated that the inferior part of the pituitary contained three times more corticotropic cells than the superior part (mean density 18.0% vs 6.0%) and the anterior part twice as many as the posterior part (mean density 12.3% vs 6.8%). On the horizontal plane, the pituitary was divided into eight zones, in which the mean of area was 2.5-21.0%. The maximal cell density may reach 40-60%. The use of this map should help the pathologist to recognize if there is corticotropic hyperplasia in a small pituitary fragment surgically removed from a patient with Cushing's disease. On the basis of this study, we put forward some criteria for diagnosing corticotropic hyperplasia.

Immunocytochemical localization of S-100 protein in interstitial cells of the monkey Macaca irus pineal gland.

Pineal interstitial cells of the monkey Macaca irus were shown to react with an anti-human S-100 protein antibody, using the indirect immunoperoxidase technique on sections of paraplast-embedded pineal glands. Immunoreactivity was seen in the cytoplasm of the cells, stellate in shape and intermingled with pinealocytes; the latter did not stain with the antiserum against S-100 protein. Immunoreactivity was also present in the nuclei, as was reported in various other cell types immunostained with anti-S-100 protein antibodies. The present results support the view that interstitial cells of the monkey Macaca irus pineal gland may be of astroglial origin.

Animal models of human pituitary tumors.

Three animal models of pituitary tumors were compared: the spontaneous prolactinoma in Wistar/Furth (W/Fu) rats, an estrogen-induced transplantable tumor in the Fischer rat (MtTF4), and a spontaneous prolactin transplantable tumor in the W/Fu rat (SMtTW1). The spontaneous prolactinoma in W/Fu rats is interesting in that it resembles the human prolactinoma by its morphological characteristics, its benign nature, and its secretion of prolactin alone. It may be useful to study the initial factors of tumorigenesis but it is very expensive and the variability of tumor growth makes it difficult to plan experiments. The MtTF4 tumor is an easy model to study because it is transplantable but this tumor differs from most human pituitary tumors by its induction by estrogen, its malignancy, its undifferentiated aspect and its secretion of ACTH, GH, and prolactin. The SMtTW1 tumor, a new model of transplantable tumor, is close to the human pituitary tumor because the initial tumor is spontaneous, the transplanted tumors are benign and well differentiated. They secrete prolactin only. These transplantable tumors are valuable for studying the factors of growth. Since no single tumor system is a perfect model, researchers have to work on different models each of which is appropriate for investigating specific problems.

The TSH secretion in the human pituitary adenomas.

TSH secretion by a pituitary tumor is very rare (2%) and it is often associated with another hormone: GH or PRL essentially. We present here nine tumors in which the TSH secretion was proved by immunocytochemistry (ICC) and by RIA in the tumor extracts, in the serum and in the culture medium. Four tumors secreted TSH only. Five tumors secreted TSH and GH predominantly. In 3 of them traces of other hormones (PRL and FSH) were also detected. The "pure" TSH adenomas were monomorphous with typical ultrastructural and immunocytochemical features. Plurihormonal TSH adenomas were bimorphous with different cells secreting GH and TSH or monomorphous with one type of cell which secreted TSH or GH or both TSH and GH. In a majority of the cases, the tumoral TSH secretion induced hyperthyroidism but in 2 patients with TSH adenoma there was euthyroidism and in another with TSH-GH adenoma there was no sign of acromegaly and GH serum levels were normal.

Somatotropic adenomas without acromegaly.

Seventeen somatotropic adenomas removed from patients without acromegaly were studied. Thirteen of them presented as a prolactinoma with amenorrhea and/or galactorrhea and elevated serum PRL levels. According to basal serum GH levels, the patients were divided into two groups, namely Group I: GH slightly elevated (n = 4) and group II: GH less than or equal to 5 micrograms/l (n = 13). The tumoral GH secretion was proved by immunocytochemistry in all cases and by intratumoral RIA, in vitro study and/or in situ hybridization in five of them. Pathological, clinical and biochemical relationships suggested two anatomoclinical aspects. In group I, the tumors were small, well-differentiated somatotropic adenomas with clinically silent GH hypersecretion. It is probably an early stage of the disease. In group II, the tumors were large with normal GH serum levels. They were poorly differentiated and secreted very low amounts of GH. In nine of them, PRL and/or PRL mRNA expression were also detected. These tumors do not secrete enough GH to increase serum levels and cause acromegaly. The somatotropic adenomas without acromegaly correspond to two anatomoclinical aspects of the disease.

The human thyrotropic adenoma: pathologic diagnosis in five cases and critical review of the literature.

Five out of 400 surgically removed pituitary tumors (frequency: 1.2%) were identified as thyrotropic adenomas according to the following criteria: identification of tumoral thyrotropic cells by immunocytochemistry and ultrastructural study; elevated serum TSH levels with decrease after surgery; and elevated concentration of TSH in the tumor. Four patients presented with hyperthyroidism and one with euthyroidism. From these five cases and 11 similar observations extracted from a critical review of literature, the morphologic, immunocytochemical, and hormonal characteristics of thyrotropic adenoma are described. Thyrotropic adenomas are more often large tumors but may also be microadenomas. The diagnosis is asserted by immunoreactivity with anti-TSH antisera. The TSH positive tumor cells are numerous. In some tumors, rare cells of other types are also found (PRL, GH, FSH, or ACTH cells). Some morphologic characteristics strongly suggest the diagnosis. The cells are often large with thin processes. They show argyrophil granulations in a slightly basophil cytoplasm and signs of secretory activity. Their secretory granules are round and small without striking variations in size, shape, and electron density. Elevated concentration of TSH in the tumor confirms the diagnosis. The presence of high serum TSH levels and a molar ratio of alpha hTSH to the whole TSH molecule greater than one are other good criteria. Decrease of TSH after surgery may not be observed in invasive tumors. TSH adenoma is most often associated with hyperthyroidism but it can also be associated with hypothyroidism or euthyroidism.

The human gonadotropic adenoma: pathologic diagnosis and hormonal correlations in 26 tumors.

Twenty-six out of 400 surgically removed pituitary tumors were identified as gonadotropic adenomas (frequency 6.25%). Morphologic, immunocytochemical, and hormonal characteristics of the gonadotropic adenoma are described. The following morphologic characteristics may suggest the diagnosis: arrangement in cords of cells showing signs of cellular activity, secretory granules, which vary in electron density, form, and size (mean diameter 150 nm) and which are numerous in the extensions near the capillaries, and a rough endoplasmic reticulum arranged in short cisternae. However, owing to the morphofunctional variations from one adenoma to another, we consider that only immunoreactivity with gonadotropin antisera proves the diagnosis. Because the material used to generate the gonadotropin antisera was purified but not pure, for precise characterization of the immunoreactivity, absorption tests with various antigens have to be performed. FSH-LH adenomas (n = 14), FSH adenomas (n = 7), and alpha-subunit adenomas (n = 5) but no LH adenomas were identified in our series. No evident morphologic difference related to the type of immunoreactivity and to the sex was found. Almost all the tumors were large with visual signs caused by suprasellar extension. A recurrence following adenomectomy was noted with a frequency of 12%. The diagnosis of gonadotropic adenoma was considered preoperatively in six out of 26 patients only, on the basis of increased serum gonadotropin levels. Correlations between hormonal levels and pathologic data were established in 17 patients. Seven tumors were associated with high serum gonadotropin levels (FSH and LH: three patients and FSH alone: four patients). In ten cases, the serum gonadotropin levels were normal but serum alpha-subunit assay had not been performed. For the pathologist systematically testing the adenomas with many antisera, gonadotropic adenomas are not as rare as for the clinician. Immunocytochemical studies with gonadotropin antisera and serum gonadotropic determination must be performed in all tumors, especially in those pituitary adenomas that appear nonfunctional.

Analysis of drugs of abuse in hair by automated solid-phase extraction, GC/EI/MS and GC ion trap/CI/MS.

In our laboratory, analysis of human hair for the detection of drugs of abuse was first performed in 1995. Initially, requests for hair analysis were few, and it is only since 1997 that these analyses have become routine. As demand grew, we developed an automatic solid-phase extraction method; the use of a robot ASPEC allowed us to drop certain fastidious manipulations, and to treat a large number of samples at a time. This method is described, along with analysis by gas-chromatography-mass spectrometry (GC/MS) in selected ion monitoring mode (SIM), for the following drugs: codeine, 6-monoacetylmorphine (6-MAM), morphine, cocaine, methadone, ecstasy (MDMA) and Eve (MDE). This requires prior derivatization with propionic anhydride. The different validation parameters, linearity, repeatability, recovery and detection limits are described, as well as the application of this method to some real cases. Analysis of these cases is also performed by an ion trap GC/MS in chemical ionization mode (GC/IT/CI/MS) in order to demonstrate the usefulness of this technique as a complement to routine analysis. Analysis by GC/IT/CI/MS indeed avoids the risk of false-positive results by the identification of metabolites.

Methadone and EDDP in hair from human subjects following a maintenance program: results of a pilot study.

A specific method has been developed for the quantitative determination of methadone (MTD) and its major metabolite, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), in hair.An amount of 50mg hair samples were incubated in 0.01M HCl overnight at 60 degrees C and deuterated internal standards of MTD and EDDP were added before extraction. Hydrolyzed solutions were extracted by automated solid-phase extraction procedure and analyzed on a gas chromatography (GC) coupled to a ion trap mass spectrometer (MS). Positive chemical ionization was used with acetonitrile as liquid reagent. The different validation parameters, linearity, repeatability, recovery and detection limits are presented. A relative standard deviation (R.S.D.) of 12 and 11% was obtained for the repeatability of MTD and EDDP, respectively. The limits of quantification (LOQ) was 0.05ng/mg for MTD and 0.2ng/mg for EDDP.A number of 26 hair samples from human subjects following a long-term MTD therapy were analyzed by this method. Blood samples of these subjects were analyzed with a routine method using a liquid-liquid extraction and GC/nitrogen phosphorus detector (NPD). MTD was quantified in blood and hair samples and EDDP found in 50% of the hair sample.A comparison was made between the concentrations found in blood or in hair and the dose administrated. This study could demonstrate that there is no relation between the administrated dose and MTD or EDDP concentrations in hair.

Analysis of methaqualone in biological matrices by micellar electrokinetic capillary chromatography. Comparison with gas chromatography-mass spectrometry.

The analysis of methaqualone (MTQ) in biological matrices by capillary electrophoresis (CE) is described. This methods uses liquid-liquid extraction and micellar electrokinetic capillary chromatography (MECC), an operation mode of CE. Separations are made using a 25 cm long capillary and a borate/phosphate buffer at pH 8.2. Using gas chromatography with mass spectrometry detection (GC-MS) as reference method, MTQ has been analyzed in urine, blood, gastric content and hair. For hair analysis, supercritical fluid extraction was compared with liquid-liquid extraction. Linearity was established in urine and blood between 0.25 and 10.0 micrograms/ml. MTQ recovery from blood was estimated at 60%. The limit of detection of this method in urine is about 0.10 microgram/ml. Drawbacks and advantages of MECC over GC-MS are discussed.

Acetylcodeine as a marker of illicit heroin in human hair: method validation and results of a pilot study.

Acetylcodeine (AC), which is an impurity of illicit heroin synthesis, was suggested as a marker of heroin abuse. A procedure for simultaneous quantitation of 6-monoacetylmorphine (6-MAM), which is the major metabolite of heroin, morphine, codeine, and AC in hair was developed. Fifty-milligram hair samples were incubated in 0.01 M HCl overnight at 60 degrees C. The resulting hydrolyzed solutions were extracted by an automated solid-phase extraction procedure and drugs were analyzed by gas chromatography-mass spectrometry in selected ion monitoring mode (SIM). This required prior derivatization with propionic anhydride. Different validation parameters, such as linearity, intra-assay accuracy, extraction recoveries, and limit of quantitation, were described. Seventy-three hair samples from heroin abusers and 43 hair samples from subjects who had completed a heroin-maintenance program were analyzed. AC was detected in 92% of the first sample group and in only 12% of the second sample group. In the two groups, about 98% of AC-positive samples were found. These results prove that AC can be considered as a suitable marker of illicit heroin use, along with 6-MAM detection.