Electron Capture Gas-liquid Chromatography Research Articles

Prenatal dichlorodiphenyldichloroethylene (DDE) exposure and neurodevelopment: A follow-up from 12 to 30 months of age

In order to evaluate the persistency of the association between DDE and infant neurodevelopment we assessed mental and psychomotor development between 12 and 30 months of age in an ongoing cohort in Mexico. A total of 270 singleton children without perinatal asphyxia diagnosis, with a birth weight ≥2 kg, mothers > 15 years of age with organochlorine maternal serum levels measured at least in one trimester of pregnancy, and who were evaluated at least in two of the four visits at 12, 18, 24 and 30 months of age, were included in this report. The Spanish version of Bayley Scales of Infant Development II (BSID_II; Bayley, 1993) was administered to the children and Psychomotor Development Index (PDI) and Mental Development Index (MDI) were calculated. Information about stimulation at home was measured using the Home Observation of Measurement of the Environment (HOME) at 6 months, and breastfeeding history was obtained through direct interviews with the mothers. Maternal serum DDE levels were determined during pregnancy by means of electron capture gas–liquid chromatography. The association between DDE prenatal exposure and neurodevelopment was estimated using separate generalized mixed effects models. Our results suggest that the association between prenatal DDE and infant neurodevelopment does not persist beyond 12 months of age even after adjusting for known risk factors for neurodevelopment. In addition, we observed an interaction between early home stimulation and mental improvement at 24 and 30 months of age ( p < 0.001). The association of DDE with infant neurodevelopment seems to be reversible. However, we cannot rule out that other DDT metabolites may play a role in neurodevelopment.

Dichlorodiphenyldichloroethylene exposure during the first trimester of pregnancy alters the anal position in male infants.

Anogenital distance (AGD) at birth is regarded as a useful measurement that reflects the prenatal androgenic status in rodents. However, the impact of xenoantiandrogens on human development is largely unknown. The aim of this study was to evaluate the potential antiandrogenic impact of prenatal DDT metabolites (p,p'-DDE and p,p'-DDT) exposure on infant AGD, using a non-age-dependent anal position index (API). As part of an ongoing perinatal cohort study on the effects of organochlorine pesticides in children's neurodevelopment, we conducted a cross-sectional study in 71 infants (37 males and 34 females). Maternal serum levels of DDT metabolites (p,p'-DDE and p,p'-DDT) before and during each trimester of pregnancy were determined by electron capture gas-liquid chromatography. During postnatal home visits at 3, 6, and 12 or 18 months of age, the children's weight and API were evaluated. Multiple lineal regression models were used to estimate the potential endocrine disruptor activity of prenatal p,p'-DDE exposure. Boys had significantly higher API values than girls (0.6 versus 0.5; P < 0.001). Only among boys, a doubling increase of maternal p,p'-DDE serum levels during the first trimester of pregnancy, were associated with a significant reduction of API (beta=-0.02; P= 0.02). No effect of p,p'-DDT on AGD was observed. Evidence of the effect of prenatal p,p'-DDE on external genital differentiation is scarce and not consistent in the literature. Further studies are needed to confirm a hormonal disruptive effect on the development of external genitalia, due not only to p,p'-DDE but also due to other antiandrogenic persistent compounds.

Organchlorines Exposure During First Trimester of Pregnancy and Its Effect on Anogenital Distance in Mexico

ISEE-227 Objective: To evaluate the impact of p,p′-DDE, p,p′-DDT, and HCB prenatal exposure on anogenital distance (AGD), a potential marker for androgenic fetal function. Material and Methods: We conducted a cross-sectional study in a sample (n = 71 of 382 births) pertaining to an ongoing cohort study evaluating the effects of organochlorine pesticides on children neurodevelopment. Serum samples from the mothers were obtained during the first trimester of pregnancy to determine organochlorine pesticides by electron capture gas-liquid chromatography. We used the anal position index as an indicator of anogenital distance. We measured the distance between the center of the anus and the coccyx (anococcygeal distance) and the distance between the center of the anus and the posterior base of the scrotum for boys and the fourchette for girls (perineal distance). We added anococcygeal and perineal distances to calculate the coccyx-scrotum and coccyx-fourchette distances. The anal position index was calculated as the perineal distance to coccyx-scrotum ratio for boys and perineal distance to coccyx-fourchette distance for girls. Results: Multivariate analysis showed that only maternal p,p′-DDE serum levels at first trimester of pregnancy were associated with a significant and differential reduction of anal position index (β = −0.015; P = 0.03) in boys (P for interaction = 0.06), suggesting the presence of antiandrogenic effects. No significant associations were observed in girls. Conclusions: To our knowledge this is the first published study that evaluates and provides evidence about the hormonal disrupting effects of prenatal DDE exposure in children; however, further studies in larger populations are needed to confirm this finding and to validate anal position index as a marker of antiandrogenic effects.

Estrogenic microenvironment generated by organochlorine residues in adipose mammary tissue modulates biomarker expression in ERα-positive breast carcinomas

IntroductionBreast cancer is the most frequent malignant disease in women. Exposure to estrogens throughout a woman's life is a risk factor for the development of breast cancer. Organochlorine compounds (OCCs), such as pesticides and polychlorinated biphenyls, are persistent lipophilic chemicals identified as endocrine disruptors, mainly with estrogenic effects. To test the hypothesis that the amount and quality of organochlorine residues in adipose tissue adjacent to breast carcinoma affect the biological behavior of the tumor, we studied biomarker expression in breast carcinoma and the OCC body burden in patients from an urban area adjacent to Paraná fluvial system, Argentina.MethodsThe studied patients were 55 women who had undergone excision biopsies of a breast lesion diagnosed as invasive breast carcinoma. Analysis of OCC residues in breast adipose tissue was conducted by electron-capture gas–liquid chromatography. Estrogen receptor alpha (ERα), progesterone receptor (PR) and proliferative activity (Ki-67) levels were measured in paraffin-embedded biopsies of breast tumors by immunohistochemistry.ResultsAll patients had high levels of organochlorine pesticides in their breast adipose tissue. The most frequently detected compounds were p,p'-dichlorodiphenyldichloroethylene, hexachlorobenzene and β-hexachlorocyclohexane. When the whole sample was analyzed, no correlation between ERα or PR expression and OCC levels were found. In the subgroup of ERα-positive breast carcinoma patients, however, there was a positive correlation between PR expression (an estrogen-induced protein) in the neoplastic cells and OCC levels in adipose tissue surrounding the tumor. More significantly, all the ERα-positive breast carcinomas from postmenopausal women exhibited high proliferation when organochlorine levels in the surrounding adipose tissue reached levels higher than 2600 ppb. No associations were found between the organochlorine body burden and any other marker of tumor aggressiveness, such as node involvement or tumor size.ConclusionThe present results support the hypothesis that organochlorine residues in adipose tissue adjacent to breast carcinoma generate an estrogenic microenvironment that may influence the biological behavior of the tumor through ERα activation and ERα-dependent proliferation. These findings may have therapeutic implications, since interference between organochlorine compounds and hormonal therapy could be expected to occur.

Comparative Single-Dose Pharmacokinetics of Clonazepam following Intravenous, Intramuscular and Oral Administration to Healthy Volunteers

The objective was to assess the single-dose pharmacokinetics of clonazepam following i.m., p.o. and i.v. administration. In an open-label, three-way crossover study, 12 healthy volunteers were randomized to receive a single dose of 2 mg clonazepam either by the i.m., p.o. or i.v. route. Serial blood samples were collected up to 120 h after drug administration. Plasma concentrations of clonazepam were determined by electron-capture gas-liquid chromatography. The absorption rates of clonazepam after i.m. and p.o. administration of clonazepam were significantly different from each other, as reflected by the respective mean values of maximum plasma concentration (C_max 11.0 vs. 14.9 ng·ml^–1) and time to reach maximum concentration (t_max 3.1 vs. 1.7 h). Secondary plasma peaks of clonazepam were observed in 9 volunteers after i.m. injection (C_max 9.9 ng·ml^–1; t_max 10.4 h). A comparison of the area under the plasma concentration-time curves (AUC) shows that the i.m. route is equivalent to the oral route (AUC_0–∞ 620 vs. 561 ng·h·ml^–1). Clonazepam was almost completely absorbed after i.m. and p.o. administration, as shown by the mean absolute bioavailability of 93 and 90%, respectively. No significant differences existed between the elimination half-lives (i.v. 38.0 h; i.m. 43.6 h; p.o. 39.0 h). The average clearance and volume of distribution (V_Z) were 55 ml·min^–1 and 180 liters, respectively. In conclusion, the observed differences in C_max and t_max after i.m. and p.o. administration were consistent with a slower absorption rate of clonazepam after i.m. injection. The systemic exposure to clonazepam was not affected by the route of extravascular administration. Statistical evaluation of these kinetic data showed differences in the absorption rate, so that clonazepam given by the i.m. route is not bioequivalent to the oral route. On the basis of the results of this study, we would recommend the same i.m. and p.o. dose in epileptic patients, but therapeutic response would be expected to be less predictable and to occur later in the case of i.m. administration.

Differentiation of sarcoidosis from tuberculosis by use of electron capture gas-liquid chromatography.

To explore further the possible etiologic role of mycobacteria in the development of sarcoidosis, we measured free, nonbound tuberculostearic acid (TSA, 10-methyloctadecanoic), a component of mycobacteria, in the sera of subjects with sarcoidosis or active untreated pulmonary tuberculosis and in healthy controls by use of frequency-pulsed electron capture gas-liquid chromatography (FPEC-GLC). The selective analytic system is capable of measuring as little as 15-fmol quantities of free, nonbound TSA in serum and cerebral spinal fluid. We found that TSA was present in the sera of all subjects with Mycobacterium tuberculosis (n = 10) but was undetectable in subjects with sarcoidosis (n = 15) and in healthy controls (n = 15), thereby suggesting that if sarcoidosis is caused by a mycobacterial organism, TSA is not produced or does not gain access to the systemic circulation in quantities sufficient for measurement. However, in the course of the studies we found that a peak, designated p11, was elevated in the sera of all subjects with acute sarcoidosis (n = 4). Also, a peak designated p3 was reduced significantly in all subjects with acute and chronic sarcoidosis and absent in subjects with M. tuberculosis compared with healthy controls. Both peaks were later shown by chemical analysis and mass spectral studies to be carboxylic acids not previously associated with specific disease entities. Follow-up detailed studies will be needed to determine if quantitation of these unique carboxylic acids will be useful in differentiating sarcoidosis from other disorders.

Detection of malignancy-associated metabolites in the sera of cancer patients by electron capture gas chromatography.

A reliable test that detects malignancy and indicates response to therapy is needed. Frequency-pulsed electron-capture gas-liquid chromatography (FPEC-GLC), a selective analytical technique that is sensitive to 15 fmol quantities of metabolites, was used to analyse derivatised acidic chloroform extracts of sera from patients with biopsy-proven cancer, non-malignant infectious and non-infectious disease, and healthy controls. Two peaks designated P1 and P10, not found in serum from healthy controls (n = 7) or patients with non-malignant disease (n = 85), were detected in biopsy-proven samples (n = 52) from cancer patients. P1 and P10 were later shown by chemical and mass spectral studies to be carboxylic acids. When one or both of these peaks were detected in the sera of non-treated patients they were always associated with malignancy. In patients responding to therapy, a reduction or disappearance of these peaks was observed. Further, it was noted that P10 persisted or increased in sera of patients with progressive cancer not responding to therapy. We conclude that this test has potential in diagnosis and for following the response of the disease to therapy.

Intranasal Absorption of Flurazepam, Midazolam, and Triazolam in Dogs

Intranasal delivery of flurazepam, midazolam, and triazolam was studied in a dog model as a possible alternate route of drug administration for treatment of insomnia. Four beagles received each hypnotic by both intranasal and oral routes on two separate occasions. Plasma concentrations for each hypnotic after dosing were measured by electron-capture gas-liquid chromatography. The mean intranasal absorption rates (tmax) of flurazepam, midazolam, and triazolam were 1.7, 2.0, and 2.6 times faster, respectively, compared with oral dosing. The mean dose-normalized peak concentrations (Cmax) after intranasal delivery were 16.4, 2.9, and 3.4 times higher, respectively, versus oral administration. The mean dose-normalized AUCs estimated for these compounds after nasal administration were 2.4−, 2.5−, and at least 2-fold larger than after oral administration for midazolam, triazolam, and flurazepam, respectively. If these observations can be extrapolated to humans, the faster absorption achieved by the intranasal route would appear to benefit insomniacs characterized by difficulty in falling asleep because of an anticipated faster sedative effect onset. The higher peak concentrations and larger amounts absorbed in the case of intranasal midazolam and triazolam delivery may lead to dose reduction.

Rapid diagnosis of tuberculous meningitis by frequency-pulsed electron-capture gas-liquid chromatography detection of carboxylic acids in cerebrospinal fluid

The frequency-pulsed electron-capture gas-liquid chromatography technique described previously by Brooks et al. was modified and applied to the studies of coded and routine clinical specimens. Uncentrifuged cerebrospinal fluid (2 ml) was extracted under acidic conditions, derivatized, and analyzed by frequency-pulsed electron-capture gas-liquid chromatography on large-bore fused silica polar and nonpolar capillary columns. The frequency-pulsed electron-capture gas-liquid chromatography profile of carboxylic acids (C2 through C22) along with identification of tuberculostearic acid, established by retention time comparison of derivatized tuberculostearic acid and derivatized sample extract, strongly suggests the presence of Mycobacterium tuberculosis in patients with lymphocytic meningitis. Results from 41 coded cases and 75 clinical cases showed that the frequency-pulsed electron-capture gas-liquid chromatography test had a specificity of 91% and a sensitivity of 95%.

Analyses of fermentation products of Listeria species by frequency-pulsed electron-capture gas–liquid chromatography

Aerobic fermentation broths of eight Listeria monocytogenes strains, two or more strains of the remaining six Listeria species, and one strain of Jonesia denitrificans were examined by frequency-pulsed electron-capture gas-liquid chromatography for carboxylic acids, alcohols, amines, and hydroxy acids. All species produced acetic, isobutyric, butyric, isovaleric, phenylacetic, lactic, 2-hydroxybutyric, 2-hydroxyvaleric, and 2-hydroxyisocaproic acids. Propionic acid was not formed, and traces of isocaproic acid were observed. Of the alcohol and amine derivatives observed, only acetylmethylcarbinol, butylamine, and putrecine were identified. Recognition of the products of glucose and amino acid metabolism serves to further characterize the members of the genus Listeria both taxonomically and physiologically.

Chlorinated hydrocarbon levels in human serum: Effects of fasting and feeding

Twenty healthy adult humans had serum samples drawn on four occasions within a 24-hr period: after a 12 hr overnight fast, 4-5 hr after a high fat breakfast, at midafternoon, and the next morning after another 12 hr fast. Nonfasting samples had 22% to 29% higher mean concentrations (p less than 0.05) than did fasting samples for polychlorinated biphenyls (PCBs, 4.81 vs 3.74 ng/g serum wt), hexachlorobenzene (HCB, 0.163 vs 0.134 ng/g serum wt), and p,p'-dichlorodiphenyl-dichloroethylene (p,p'-DDE, 6.74 vs 5.37 ng/g serum wt) measured by electron capture gas liquid chromatography. Total serum lipids were estimated from measurements of total cholesterol, free cholesterol, triglycerides, and phospholipids and were 20% higher in nonfasting samples than in fasting samples (7.05 g/L vs 5.86 g/L). When PCBs, HCB, and p,p'-DDE concentrations were corrected by total serum lipids, results from fasting and non-fasting samples were not statistically different. Because of the differences in these chlorinated hydrocarbon concentrations observed with different sample collection regimens, meaningful comparison of analytical results requires standardizing collection procedures or correcting by total serum lipid levels.

Pharmacokinetics of the Newer Benzodiazepines

The assay methods used to determine the concentrations of the newer benzodiazepines include electron-capture gas-liquid chromatography, high performance liquid chromatography with ultraviolet detection, gas chromatography-mass spectrometry, radioassay and radioreceptor assay. The method used frequently is the highly sensitive and specific electron-capture gas-liquid chromatography. Other methods are associated with limitations. The triazolo- and imidazolebenzodiazepines differ structurally from the 'classical' benzodiazepines such as diazepam, and offer distinct differences in pharmacological activity and in time-course of effect. Alprazolam and triazolam, both 1,4-triazolobenzodiazepines, have high affinities for the benzodiazepine receptor as do midazolam and loprazolam, which are 1,4-imidazolebenzodiazepines. Absorption is characteristically rapid, with peak alprazolam and triazolam concentrations occurring within 1 hour after oral administration. Sublingual administration results in peak alprazolam and triazolam concentrations that are higher and occur earlier than with the oral route. The volume of distribution of alprazolam and triazolam is approximately 1L. Alprazolam is 70% bound to plasma proteins and the extent of binding is independent of concentration. Similarly, triazolam is approximately 85% bound to plasma proteins, variability in binding being explained by variations in alpha 1-acid glycoprotein concentration. The 1,4-triazolo ring prevents the oxidative metabolism of the classical benzodiazepines which results in formation of active metabolites with long elimination half-lives. Alprazolam is extensively metabolised: 29 metabolites have been identified in the urine, and its major metabolite, alpha-hydroxyalprazolam, has pharmacological activity. alpha-Hydroxyalprazolam and 4-hydroxyalprazolam are detectable in plasma in amounts which account for less than 10% of the administered dose. Mean alprazolam elimination half-life in healthy adult subjects ranges from 9.5 to 12 hours; liver disease prolongs alprazolam elimination, but renal insufficiency does not. Triazolam also undergoes oxidation and subsequent glucuronidation. alpha-Hydroxytriazolam is the major metabolite, in addition to which 4-hydroxyalprazolam and alpha-4-hydroxytriazolam have been identified in plasma and urine. The elimination half-life of triazolam ranges between 1.8 and 5.9 hours, while that of the conjugated metabolites is short, approximately 3.8 hours. Accumulation of triazolam or its metabolites after multiple doses does not occur. Liver disease prolongs triazolam elimination from the body, but renal disease does not.(ABSTRACT TRUNCATED AT 400 WORDS)

An international intercalibration for methylmercury in biological tissue

AbstractAn intercalibration exercise between 13 laboratories from seven countries was conducted for comparing the methylmercury measurement techniques for marine biological tissues. Analyses have been conducted on two sets of samples: a fish muscle and a mussel soft tissue. Most of the participating laboratories performed six replicate analyses, allowing statistical comparisons. Various analytical techniques have been used, including cold vapour atomic absorption spectrophotometry (CVAA), electron capture gas liquid chromatography (GCEC), neutron activation (NAA), and inductively coupled plasma–isotopic dilution mass spectrometry (ICPIDMS). All of these methods offer similar results. They allow us to define consensus values which seem good estimates of the real concentrations. In addition the results show, for most of the participating laboratories, good accuracy and precision in the determination.

Transesterification of phospholipids or triglycerides to fatty acid benzyl esters with simultaneous methylation of free fatty acids for gas-liquid chromatographic analysis.

A novel method is presented for transesterification of fatty acid esters in phospholipids and triglycerides to benzyl esters while simultaneously recovering free fatty acids as methyl esters. Transesterification is catalyzed by 0.2 M (m-trifluoromethyl phenyl)trimethyl ammonium hydroxide in methylene chloride, 10% (v/v) benzyl alcohol, and 1% (w/v) potassium tert-butoxide, and is complete in 30 min at room temperature. Methyl esters of all common fatty acids separate from the benzyl esters formed from phospholipids. This method has broad utility and is applicable to the formation of esters optimized for detection by absorbance or fluorescence (high performance liquid chromatography), electron capture (gas-liquid chromatography), or negative ion chemical ionization (gas-liquid chromatography-mass spectrometry).

Quantitation of flurazepam and three metabolites by electron capture gas liquid chromatography.

Flurazepam and three of its metabolic products (desalkyl, hydroxyethyl, and aldehyde metabolites) can be simultaneously quantitated without derivatization by gas chromatography with electron capture detection. After addition of a suitable internal standard, unknown biological samples and calibration standards are extracted at neutral pH into benzene/isoamyl alcohol. The reconstituted extract is chromatographed at 275 degrees C with a 10% OV-101 liquid phase, which allows resolution of all 5 compounds. In some cases a 1% OV-225 liquid phase is used for quantitation of hydroxyethylflurazepam. The method is sufficiently sensitive and reproducible for use in clinical and experimental pharmacokinetic studies.

Alprazolam pharmacokinetics in women on low-dose oral contraceptives.

Sixteen women chronically using low-dose estrogen-containing oral contraceptive steroids (OCs) and 23 drug-free control women received a single 1-mg oral dose of alprazolam. Multiple plasma samples drawn during 48 hours after the dose were analyzed by electron-capture gas-liquid chromatography. There were no significant differences between controls and oral contraceptive users in alprazolam volume of distribution (1.27 versus 1.39 L/kg), elimination half-life (11.9 versus 12.3 hours), total clearance (1.36 versus 1.39 mL/min/kg), or total area under the plasma concentration versus time curve (227 versus 243 ng/mL X hr). Alprazolam free fraction in plasma was slightly but significantly greater in the oral contraceptive group as opposed to the control group (28.4 versus 27.0% unbound), respectively. However, comparison of free clearance between groups revealed no significant difference (4.61 versus 4.89 mL/min/kg, respectively). Thus, low-dose estrogen-containing oral contraceptives do not significantly influence the metabolic clearance of alprazolam.

Ruckstandsanalyse von Pyrethroid-Insecticiden in Getreide, Mahlerzeugnissen und Brot

A procedure is described for the residual analysis of eight pyrethroid insecticides at levels of 2-5 micrograms/kg. Residues are extracted from cereal grains, flour or bread with a mixture of acetonitrile/water (2 + 1) and are partitioned into petroleum ether. Clean-up is performed by gel permeation chromatography on Bio-Beads S-X3 and an additional Florisil column. Electron capture gas liquid chromatography on a non-polar SE-30 capillary column separates the isomers of the compounds. Under the conditions used in the experiments with cyfluthrin, cypermethrin, deltamethrin, fenvalerate, and permethrin, the compound levels in rye and wheat did not decrease significantly. Losses during milling and baking were small. Consequently, pyrethroid insecticides remain effective in grain stored over a long period of time. However, considerable residues result in the milled fractions as well as in different types of bread.

Disposition of d-fenfluramine in lean and obese rats

The anorectic drug D-fenfluramine (D-F) was administered as single i.v. doses of 1.25 and 6.25 mg/kg to lean female Sprague-Dawley and lean and obese female Zucker rats. Blood samples were collected serially and analysed by electron capture gas-liquid chromatography for D-F and its main metabolite, D-norfenfluramine (D-NF). At the lowest dose the disappearance of D-F followed an apparent first-order process with mean elimination half-life (T1/2) of approximately 2 h in female Sprague-Dawley and 4 h in lean and obese Zucker rats. Mean absolute steady-state volume of distribution (Vss) was the same in the lean female of both strains but total clearance (Cl) was significantly lower in the Zucker rats. Therefore elimination T1/2 of D-F was longer in female Zucker than Sprague-Dawley animals. Obese rats presented lower relative Cl and Vss but no change in absolute Cl and Vss and elimination T1/2 of the drug. Intra- and inter-strain differences were observed in hepatic microsomal protein and P-450 content. As in the case of D-F the elimination T1/2 of D-NF was also longer in Zucker than Sprague-Dawley rats. No differences were observed between lean and obese rats but in all cases the elimination T1/2 of the metabolite was much longer than that of its parent drug. After larger doses (6.25 mg/kg) the kinetics of the drug were not linear. The apparent Cl declined changing the metabolite-to-parent drug ratios in all types of rats, but more evidently in Zucker than Sprague-Dawley rats and in obese than lean animals. Inter- and intra-strain differences in D-F and D-NF kinetics should be considered in neurochemical studies of the drug and extrapolation of data across animal species requires consideration of dose dependence in the rat.

Alprazolam Kinetics Following Sublingual and Oral Administration

Thirteen healthy volunteers received 1 mg of alprazolam, as the commercially available oral tablet, by sublingual and oral routes on two occasions in random sequence. Plasma alprazolam concentrations during 48 hours after each dose were measured by electron-capture gas-liquid chromatography. The peak plasma concentration after sublingual dosage was higher than after oral administration (17.3 vs. 14.9 ng/ml), and the time of peak concentration following sublingual administration was reached (1.17 vs. 1.73 hours after dose). However, these differences did not reach statistical significance. The mean total area under the plasma concentration curve for sublingual administration was slightly but not significantly larger than that following oral dosage (203.7 vs. 194.4 hr.ng/ml) and no significant differences between sublingual and oral dosage were found for elimination half-life (11.7 vs. 11.8 hours) or for clearance (86.4 vs. 92.4 ml/min). Thus, alprazolam absorption following sublingual administration is as rapid as after oral dosage on an empty stomach, and completeness of absorption is comparable. In clinical terms, sublingual and oral dosages of alprazolam are likely to be therapeutically equivalent. The sublingual route may be a useful alternative for panic disorder patients who cannot swallow pills or for those who do not have access to a liquid at the time of dosing.

Disposable reversed-phase chromatography columns for improved detection of carboxylic acids in body fluids by electron-capture gas-liquid chromatography.

Disposable reversed-phase chromatography columns were tested for their effectiveness in removing unreacted trichloroethanol (TCE) from derivatized samples for gas-liquid chromatography analysis. Derivatized acidic chloroform extracts of saponified whole cells of Mycobacterium species, spent culture media, and derivatized acidic chloroform extracts of serum and cerebrospinal fluids from patients with tuberculous meningitis were tested. Samples were added to preconditioned reversed-phase chromatography columns, and various solvents and solvent mixtures were tested to determine maximum recovery of the TCE derivatives. With this procedure, we were able to quickly remove the TCE reagent and efficiently recover TCE-derivatized carboxylic acids. Use of these columns improved the reagent cleanup procedure, simplified the derivatization step, permitted increased detection of trace components, such as tuberculostearic acid, in body fluids, and improved the selectivity of the procedure for detection of carboxylic acids.