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Objective The purpose of this article is to provide an overview of the current research on hallucinogen induced psychiatric disorders. In addition to LSD and psilocybin hallucinogens of biologic origin are increasingly used by adolescents and young adults. Methods Relevant literature and related articles were identified by means of a computerized MEDLINE search including the years 1997 - 2007. As keywords "hallucinogen induced psychosis", "hallucinogen induced flashback", "hallucinogen persisting perception disorder (HPPD)" were used. Finally, 64 journal articles and books out of 103 were included in the review. Results Acute psychotic syndromes in adolescents are rarely due to intoxications with hallucinogenic drugs. However, clinical relevance of flashback phenomena as post-hallucinogenic psychiatric disorder has to be disputed. Because of the high popularity of biogenic hallucinogens and LSD knowledge of intoxications and resulting psychiatric disorders as well as medical complications and therapeutical approaches are clinically important. Especially intoxications with drugs of herbal origin like tropanalcaloids play an important role in emergency situations.

A new, rapid, and precise liquid chromatographic method has been developed for simultaneous identification and quantification of amphetamine,N-methyl-3,4-methylenedioxymetamphetamine,N-ethyl-3,4-methylenedioxymetamphetamine, andN-methyl-1-(3,4-methyl-enedioxyphenyl)-2-butanamine in the presence of other constituents. The compounds were separated on a monolithic column with a gradient prepared from acetonitrile and 20mm monobasic potassium buffer at a flow rate of 1.5 mL min−1. Quantitation was performed with metoclopramide as internal standard. Use of different flow rates was investigated and enabled reduction of the separation time from 11 to 3.5 min for seven substances. The method was then applied to ten seized tablets to identify and quantify their active ingredients.

In order to evaluate the neurobiological mechanism causing the psychogenic effects of methylenedioxy-derivatives of amphetamine, the carbon-11 labeled analogues of 3,4-methylenedioxymethamphetamine (MDMA),2 and 2,N-dimethyl-4,5-methylenedioxyamphetamine (MADAM-6)4 were prepared for application in in-vivo PET studies by methylation of 3,4-methylenedioxyamphetamine (MDA)1 and 2-methyl-4,5-methylenedioxyamphetamine3 with [11C]CH3I. The radiochemical yield was determined in dependence on time, temperature and amount of precursor. The best conditions for a fast labeling reaction with carbon-11 on a preparative scale were found to be a reaction time of 10 min using 1 mg of the corresponding dimethyl-precursors1 or3, thus obtaining radiochemical yields of 60% (based on produced [11C]CH3I). Biodistribution studies were performed in rats, a high brain to blood ratio of 7.5 was observed for [11C]MDMA in contrast to a ratio of 3.7 for [11C]MADAM-6.

Near-infrared spectroscopy (NIRS) was used to determine acetylsalicylic acid (ASA) in three different effervescent tablet formulations. The nominal ASA concentrations were 14.9% in the single substance formulation (ASA Mono), 17.4% in the combination with ascorbic acid (ASA + C) and 8.7% in the combination with paracetamol and ascorbic acid (ASA Combi). In each case the tablet matrix was composed of seven excipients typical of effervescent tablets. All three formulations were measured as intact tablets in diffuse transmittance and reflectance and as powdered tablets in diffuse reflectance. Calibration was carried out by partial least square (PLS) regression of second derivative spectra. High-performance liquid chromatography (HPLC) was used as the reference method. The relative standard errors of calibration (RSEC) achieved for the three NIR methods were between 1.20 and 2.01% for ASA Mono, between 1.91 and 2.21% for ASA + C and between 2.41 and 4.50% for ASA Combi. The results obtained in transmittance mode were comparable with those obtained in reflectance mode, which is normally used in NIRS. In the test sets of ASA Mono and ASA + C relative root mean square (RRMS) values between 2.21 and 3.13% were obtained. The three NIR methods applied are thus suitable for the quantitative determination of ASA in effervescent tablets and have the advantage over HPLC of being rapid and simply carried out with little sample preparation; they are nondestructive and do not require any environmentally harmful reagents.

N-[11C]methyl-1-(1,3-benzodioxol-5-yl)-2-butanamine ([11C]MBDB) 3 was prepared by methylation of the demethyl precursor BDB with [11C]CHI. The radiosynthesis was optimized with regard to temperature, reaction time and amount of precursor, best results (i.e., 84% radiochemical yield, based on [11C]CH3I activity) were obtained using 3 mg BDB at a reaction temperature of 130 °C in 8 minutes. With respect to a facilitated workup routine, productions were performed with 0.6 mg BDB at 110 °C for 10 minutes, yielding more than 50% of 3. The radiochemical purity of the final tracer solution was >98%, the specific activity was determined to be 300 GBq/μmol (8000 Ci/mmol). Biodistribution, studies in rats showed two major metabolic pathways as indicated by an increasing liver uptake (9.1% ID/organ at 5 minutes to 21% ID/organ at 30 minutes) and a high urine activity (up to 16% ID/g). In brain tracer uptake was more than 1%, with a brain to blood ratio of almost 12 resulting from a very rapid blood clearance of 3.

Hyperici Oleum (St. John's wort oil) used in wound healing contains no hypericin. By using the sunlight maceration method described in the supplement to DAB 6 (EB 6), lipophilic breakdown products of this compound are obtained which lend the oil its red colour. Hyperforin, which is responsible for the oil's therapeutic activity could, for the first time, be identified and quantitatively determined by TLC and HPLC after solid-phase extraction. The stability of hyperforin is limited; sufficient shelf-life could only be achieved by hot maceration of dried flowers with eutanol G and storage in the absence of air. By gradient HPLC further polar hyperforin analogues were detected in those St. John's wort oils in which hyperforin had decomposed. At the same time flavonoids and xanthones could be identified. A procedure for the quantitative determination of flavonoids in St. John's wort was validated. The action of light during preparation of the oil led to a rise in the content of flavonoids.

The purpose of this article is to provide an overview of the current research on hallucinogen induced psychiatric disorders. In addition to LSD and psilocybin hallucinogens of biologic origin are increasingly used by adolescents and young adults.Relevant literature and related articles were identified by means of a computerized MEDLINE search including the years 1997 - 2007. As keywords "hallucinogen induced psychosis", "hallucinogen induced flashback", "hallucinogen persisting perception disorder (HPPD)" were used. Finally, 64 journal articles and books out of 103 were included in the review.Acute psychotic syndromes in adolescents are rarely due to intoxications with hallucinogenic drugs. However, clinical relevance of flashback phenomena as post-hallucinogenic psychiatric disorder has to be disputed. Because of the high popularity of biogenic hallucinogens and LSD knowledge of intoxications and resulting psychiatric disorders as well as medical complications and therapeutical approaches are clinically important. Especially intoxications with drugs of herbal origin like tropanalcaloids play an important role in emergency situations.

A new method of an on-line coupling of TLC and FTIR spectroscopy is introduced. By the combination of a computer controlled x—y-stage with a “diffuse reflectance unit” and an FTIR spectrometer using commercially available GC-IR software it is possible to obtain chromatograms of a TLC separation. The chromatograms can be generated both frequency dependent as spectral windows of a certain range and frequency independent as Gram-Schmidt trace. During the measurement the series of interferograms are saved on a hard disk, so that the desired TLC-FTIR spectra can be immediately computed after the end of the measurement. If necessary, a stationary measurement can be performed at the position of maximum substance concentration with high resolution and coaddition of interferograms. The quality of the TLC-FTIR spectra is sufficient for identification of unknown substances and discrimination of closely related substances. There are different ways to present the huge amount of received data: as a 3-dimensional stacked plot of the measured spectra, as horizontal sections through that stacked plot, as a contour plot, with which a rapid check of peak purity is possible, or as frequency dependent chromatograms at any wavelength of interest.

The purpose of this study was a) to present a facilitated method for the preparation and workup of [11C]d-threo-methylphenidate ([11C]d-threo-MP) (a ligand that was shown to bind selectively to the presynaptic dopaminergic transporters) from [11C]methyliodide ([11C]CH3I), b) to demonstrate that the ligand can as well be produced by an alternative labeling method employing [11C]diazomethane as the labeling agent and c) to present biodistribution data for this tracer obtained in rats.11C-labeling with [11C]CH3I was performed using either [d-threo-1-(2-nitrophenylsulfanyl)piperidin-2-yl]phenyl-acetic acid (d-threo-N-NPS-ritalinic acid) under addition of sodium hydroxide as base or the previously prepared sodium salt of d-threo-N-NPS-ritalinic acid. The two approaches were compared with regard to radiochemical yield and purification procedures needed in order to obtain a sufficiently pure tracer solution for human use. For the alternative reaction pathway using [11C]diazo-methane as the labeling agent the reaction was performed with d-threo-N-NPS-ritalinic acid. The biodistribution of [11C]d-threo-MP was determined in rats at 5, 10 and 30 min post injection of the tracer.The application of the sodium salt of d-threo-N-NPS-ritalinic acid as precursor resulted in higher radiochemical yields than the use of the free acid under basic conditions, the yields were 20 +/- 8% and 6 +/- 3%, respectively for the final isolated product (based on [11C]CH3I starting activity). The alternative labeling approach by means of [11C]diazomethane as the labeling agent was demonstrated to give radiochemical yields of 76 +/- 8% (based on [11C]diazomethane starting activity, determined by HPLC analysis of the crude reaction mixture before final work-up) within shorter process times. Based on [11C]methane starting activity both approaches result in similar yields (17% and 15%, respectively) Biodistribution studies in rats revealed a low blood activity (0.09% injected dose/g (% ID/g)) at 5 min post injection (p.i.), as well as a relatively high liver uptake (15.9% ID at 30 min) compared to a lower kidney uptake (3.2% ID at 30 min). Brain uptake was 0.9% ID/g already 5 and 10 min p.i..The application of the sodium salt of d-threo-N-NPS-ritalinic acid as precursor for the radiosynthesis of [11C]d-threo-MP reduces the amount of [11C]methanol formed from the reaction of [11C]CH3I with sodium hydroxide, that is added to generate the carboxylic anion of d-threo-N-NPS-ritalinic acid needed for labeling with [11C]CH3I. The purification process could be simplified (omission of one solid phase extraction step), resulting in an easily automated process for the production of the tracer. The preparation of [11C]d-threo-MP by means of [11C]diazomethane as the labeling agent appears to be an interesting alternative to the [11C]CH3I methods because of shorter overall process times and high labeling yields. Biodistribution data show a rapid extraction of the tracer from the blood pool. Tracer excretion seems to take place predominantly via the hepatic pathway since liver uptake at 30 min was considerably higher than kidney uptake. [11C]d-threo-MP exhibits a rapid and sufficiently high brain uptake in rats.

In order to evaluate the neurobiological mechanism causing the psychogenic effects of N-methyl-2,5-dimethoxy-4-methylamphetamine (MDOM), the11C labelled analogue was prepared for application in in vivo PET studies by the reaction of 2,5-dimethoxy-4-methylamphetamine (DOM) with [11C]CH3I. The radiochemical yield was determined in dependence on time, temperature, solvent and amount of substrate. The best conditions for fast labelling reactions with11C on a preparative scale were found to be a reaction time of 10 miutes at 110°C using 1 mg DOM in acetonitrile thus obtaining radiochemical yields of 80% (based on produced [11C]CH3I).

An efficient method to characterise complex plant extracts is described using the example of Piper methysticum Forst. (kava; Piperaceae). The method is based on the on-line coupling of high-performance liquid chromatography to a new detection technique: coordination ion spray–mass spectrometry (CIS/MS). CIS/MS is a universal, novel ionisation technique improving selectivity as well as sensitivity. Charged complexes were formed through addition of central complexing ions such as sodium, silver and cobalt. The advantages of CIS/MS detection compared with the electrospray ionisation detection are discussed. The experimental set-up and the application of this simple and robust technique is described to show the its various fields of application in the analysis of plant extracts. Copyright © 2004 John Wiley & Sons, Ltd.

This paper describes a convenient and practice method for quantitation of surfactant phospholipids (1,2-dipalmitoyl-3-sn-phosphatidyl choline [DPPC] and 1-palmitayl-2-oleyl-3-sn-phosphatidyl glycerol [POPG]) in a recombinant surfactant lyophile (Venticute) by high-performance, thin-layer chromatography (HPTLC) with video densitometry. DPPC and POPG were extracted from Venticute-lyophile using methanol. Separation from the other active ingredients and excipients was accomplished by HPTLC on silica gel F254 plates with a mixture of chloroform, methanol, glacial acetic acid, and water as development solvent. Postchromatographic derivatization by dipping in copper sulphate/phosphoric acid reagent and subsequent heating shows grey-brown bands on a light blue background. These were detected with the video densitometer in the VIS range, and with scanning densitometry at 365 nm. Linear calibration in a working range of 0.7-1.3 microg DPPC and 0.35-0.65 microg POPG was demonstrated by integrating the area under the peaks. Good results were obtained with recovery experiments. When compared to classical slit scanning densitometry, video densitometry represents a fast alternative to quantitate thin-layer chromatograms in surfactant phospholipid analysis.

A high throughput screening method for the analysis of 5-hydroxytryptamine(2A) (5-HT(2A)) receptor binding parameters has been developed, using 96-well filter plates of the Millipore MultiScreen system in combination with a MicroBeta PLUS microplate scintillation counter. MAFB filter plates (GF/B filter over a Durapore membrane) were used because of the lower nonspecific binding of the radioligand to GF/B filter material than to GF/C filters. Comparing different scintillation cocktails, highest counting efficiency and shortest equilibration time were detected with Betaplatescint, after drying the plates at 50 degrees C for 2 h. Measuring the plates without the plastic underdrain increased the counting efficiency by about 39% as compared with counting the plate with the underdrain intact. Presoaking the wells with 0.5% polyethyleneimine for 2 h reduced the nonspecific binding to the filter material by about 50%. A linear relationship of protein concentration and radioligand binding was established up to a protein concentration of 165 microg of protein/well. In the assays, 70 microg of protein/well was generally used, which has turned out to be favorable with respect to the number of counts obtained. When a higher concentration of protein was used, the period of time needed to aspirate the plate was too long because of obstruction of the filter material. Receptor-radioligand equilibration was reached after about 20 min at concentrations less than 0.05 nM [(3)H]ketanserin-HCl; at higher concentrations it was reached after about 10 min. Saturation analysis of [(3)H]ketanserin-HCl resulted in a mean B(max) of 393 fmol/mg protein and a K(D) of 2.0 nM using rat frontal cortex as a receptor source. Competition experiments with known 5-HT(2A) receptor ligands-DOB-HCl (K(i) = 59 nM), DOET-HCl (K(i) = 137 nM), DOM-HCl (K(i) = 533 nM), DMT (K(i) = 1,985 nM), and TMA-HCl (K(i) = 22,340 nM)-were in accordance with literature values.

The concentration effect of automated on-line solid-phase extraction (SPE) in combination with HPLC and very sensitive electrochemical detection was employed for the determination of N-ethyl-4-hydroxy-3-methoxy-amphetamine (HMEA, the main metabolite of the ecstasy analogue MDE), delta 9-tetrahydrocannabinol (THC) and 11-nor-delta 9-tetrahydrocannabinol-carboxylic acid (THC-COOH) in plasma and urine in comparison to a previously published psilocin assay. For the SPE either CBA (functional group: carboxypropyl)- or CH (functional group: cyclohexyl)-sorbent was used. The following separation was carried out on a reversed-phase column (LiChroCart, Superspher 60 RP select B from Merck). Depending on the hydrodynamic voltammogram of the analyzed substance the oxidation potential varied from 920 mV up to 1.2 V. In spite of using high potentials, precision and accuracy were always within the accepted statistical requirements. The limits of quantitation were between 5 ng/ml (THC, THC-COOH in plasma) and 20 ng/ml (HMEA in plasma). Advantages of on-line SPE in comparison with off-line methods were less manual effort, evidently smaller volumes (or = 400 microliters) of plasma or urine and almost always higher recovery rates (93%). The assays have been successfully proven with real biological samples and found suitable for use in routine analysis.

The aim of this study was to contribute to the characterization of the entactogen (ecstasy) substance group. The psychopathological, neuroendocrine and autonomic effects of common recreational doses of the entactogen 3,4-methylenedioxyethylamphetamine (MDE), the hallucinogen psilocybin, the stimulant d-methamphetamine and placebo were investigated in a double-blind study with healthy volunteers (n = 32). Psychological effects of the drugs were assessed by means of standardized rating scales, self assessment inventories and free descriptions. The most characteristic effects of MDE were pleasant emotional experiences of relaxation, peacefulness, content and closeness to others. However, significant stimulant and hallucinogen-like effects were also present, although the latter were weaker than the effects of psilocybin. MDE elicited the strongest endocrine and autonomic effects among the three drugs, including robust rises of serum cortisol and prolactin, elevations of blood pressure and heart rate, and a moderate, but significant rise of body temperature. The apparent contrast between psychological and autonomic effects (subjective relaxation versus physical activation) was a unique feature of the MDE state. Our findings are in line with both users' reports and results from previous experimental studies, and support the view that entactogens constitute a distinct psychoactive substance class taking an intermediate position between hallucinogens and stimulants.

Amphetamines, tryptamines, phencyclidines, tetrahydrocannabinol and substances of the ecstasy group are characterized as stimulants, hallucinogens and entactogens. The various effects of each group and their mode of action in different transmitter systems are described. 28 new compounds of the amphetamine and tryptamine series has been calculated, which exceed the hallucinogenic effects of mescaline. The different pathways of the metabolism of MDMA (ecstasy) and MDE in humans may probably explain their individual effects.

A cannabinoid pseudoreceptor model for the CB1-receptor has been constructed for 31 cannabinoids using the molecular modelling software YAK. Additionally, two CoMFA studies were performed on these ligands, the first of which was conducted prior to the building of the pseudoreceptor. Its pharmacophore is identical with the initial superposition of ligands used for pseudoreceptor construction. In contrast, the ligand alignment for the second CoMFA study was taken directly from the final cannabinoid pseudoreceptor model. This altered alignment gives markedly improved cross-validated r2 values as compared to those obtained from the original alignment with r2 cross values of 0.79 and 0.63, respectively, for five components. However, the pharmacophore alignment has the better predictive ability. Both the CoMFA and pseudoreceptor methods predict the free energy of binding of test ligands well.

Studies on the isolation, identification, quantification, and synthesis of the urinary metabolites of racemic 3,4-methylenedioxyethylamphetamine (MDE) in humans are presented. After oral administration of 140 mg of racemic MDE to healthy volunteers, the following phase I metabolites could be isolated and identified by GC/MS: unchanged racemic MDE (I), racemic 3,4-dihydroxyethylamphetamine (II), racemic 4-hydroxy-3-methoxyethylamphetamine (IIIa), racemic 3,4-methylenedioxyamphetamine (IV), racemic 3,4-dihydroxyamphetamine (V), racemic 4-hydroxy-3-methoxyamphetamine (VIa), methylenedioxyphenylacetone (IXa), 3,4-methylenedioxyhippuric acid (X), and hydroxymethoxyhippuric acid (XII). The probable intermediate metabolite 3,4-dihydroxyhippuric acid (XI) could not be detected. Therefore, two overlapping phase I metabolic pathways for racemic MDE in humans could be postulated. The first and predominant pathway leads, via ring degradation by O-dealkylation, to the corresponding 3,4-dihydroxy metabolites, which are subsequently methylated at the hydroxyl group at position 3 of the aromatic ring. The second pathway leads, via side chain degradation by N-dealkylation, to the corresponding primary amines (IV, V, and VI). Oxidative N-deamination forms the substituted phenylacetones, which are degraded to the corresponding benzoic acids. This is followed by conjugation with glycine to form substituted hippurates. The structures of all of these metabolites were confirmed by chemical syntheses, which are described in this paper. All of the metabolites containing hydroxy groups are partly excreted in a conjugated form, because the amounts of these metabolites were much higher in urine extracts after enzymatic cleavage of conjugates. Quantification of the urinary excretion by HPLC revealed that 19% of the MDE dose was eliminated as I, 31.6% as IIIa, and 2.8% as IV within 32 hr.

The widely used recreational drugs 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy) and 3,4-methylenedioxyethamphetamine (MDE, Eve) occupy an intermediate position between stimulants and hallucinogens. Besides stimulation similar to that caused by amphetamines, they usually induce a pleasant, easily controllable emotional state with relaxation, fearlessness and feelings of happiness, but they sometimes also have stronger, hallucinogenic, effects. A number of pharmacological studies support the hypothesis that these drugs make up a distinct class of psychoactive substances, which have been designated "entactogens." On the drug scene, MDMA and MDE are considered "safe." However, this view must be corrected. Complications are rare, but potentially devastating ([long-lasting anxiety and depressive syndromes in chronic users, fatalities with hyperpyrexia, rhabdomyolysis and DIC syndrome (disseminated instravascular coagulation), possible hepatotoxicity]. Moreover, the clinical relevance of animal studies showing neurotoxic effects of MDMA on central serotonergic pathways is still not clear.

Research in experimental psychosis has a long tradition extending through several stages. With the world wide abuse of psychoactive substances it came to an abrupt end. Systematic questions within this framework of research are still unresolved, and research on newly developed compounds is almost completely lacking. A review of the pharmacological and psychological effects of various psychoactive agents is provided, and results of recent experimental studies on arylalkylamines are discussed. It is argued that from a systematic as well as from a methodological viewpoint the traditional approach of experimental psychosis represents a valuable tool in psychiatric research.

A convenient HPTLC method is described for the quantification of cinchocaine hydrochloride (dibucaine) in a local anaesthetic ointment. Classical slit scanning densitometry is compared with video densitometry by avaluating the plates by line scanning and then by image analysis. For the ointment determination, detection and quantification limits in the lower nanogram range are attained, with very low coefficients of variation (about 0.06–0.2%). Whereas the results are average for scanning densitometry, the results for image analysis are very good. Cinchocaine hydrochloride was extracted from a commercial ointment with methanol. Separation from the other ingredients and excipients was accomplished by HPTLC on silica gel plates with a mixture of toluene, acetone, methanol and 25% ammonia as developing solvent. Cinchocaine hydrochloride shows blue fluorescent spots that were detected by video densitometry at 366 nm and by scanning densitometry at 312 nm. Linear calibration in the working range of 50–350 ng cinchocaine hydrochloride was demonstrated by integrating the area under the peaks. When compared to classical slit scanning densitometry, video densitometry —in combination with a rapid sample preparation-represents a fast alternative for quantifying thin layer chromatograms in cinchocaine analysis.

For in vivo receptor studies N-[11C]methyl-2,5-dimethoxy-4-bromo-amphetamine, [11C]MDOB, was synthesized by the reaction of [11C]CH3I with DOB in acetonitrile. The labelling yield was determined in dependence on amount of precursor, time and temperature of the methylation reaction. During 10 to 15 minutes 60% to 70% of [11C]MDOB has been obtained at 110°C.

The ointment bases Lanolinum, Lanae alcoholum unguentum, Zinci unguentum, Polyethylenglycoli unguentum, Unguentum leniens and Unguentum emulsificans, and the emulsifying agents Glyceroli monostearas, Polyethylenglycoli 400 stearas and Polysorbatum 20, 60, 80 were identified by HPTLC and their most important components were determined quantitatively by application of HPLC. The proposed methods of identification are more specific than those described in the monographs of the pharmacopoeias. The obtained results were compared with the nominal values listed in both pharmacopoeias as assays of these bases and emulsifiers are not mentioned, except for glyceroli monostearas.

This paper describes analytical techniques for quantitative and qualitative determination of histamine and its metabolites (N tau-methylhistamine, N alpha-methylhistamine and N alpha, N alpha-dimethylhistamine) in the pig gastric mucosa. These metabolites and N alpha-acetylhistamine, imidazolyl-4-acetic acid and N tau-methylimidazolylacetic acid were synthesized as reference compounds and analyzed by using the dansylation technique. TLC of dansylated mucosal extracts in various solvents (in situ fluorescence measurements) in combination with TLC/IR and TLC/MS transfer technique demonstrated the presence of histamine. The only metabolite was N tau-methylhistamine.

Methylation of histamine in the gastric mucosa of various species has been studied in vitro and in vivo. When gastric mucosal homogenates of rat, guinea pig, cat, dog, and pig were incubated with 14C-histamine in the presence of S-adenosyl methionine Ntau-methylhistamine was formed as the only methylated histamine derivative. Excessive concentration of Ntau-methylhistamine inhibited the formation of Ntau-methylhistamine. Pretreatment of guinea pigs with prednisolone, aminoguanidine, or pentagastrin neither influenced in vitro the formation of Ntau-methylhistamine significantly nor shifted the methylation reaction towards the side chain. Pretreatment of guinea pigs with the histamine H2-receptor blocker cimetidine significantly enhanced the formation of Ntau-methylhistamine in vitro. In pooled samples of guinea pig gastric mucosa histamine and Ntau-methylhistamine were found. Under none of these circumstances was Nalpha-methyl-or Nalpha,Nalpha-dimethylhistamine found. It is concluded that in rat (to a small extent), guinea pig, cat, dog, and pig gastric mucosa the formation of Ntau-methylhistamine is the only methylating pathway of histamine. In cases where other methylated histamine derivates (Nalpha-methyl- and/or Nalpha,Nalpha-dimethylhistamine) are found they must origin in sources other than the gastric mucosa.

Trifluoromethyl sulfonic acid in glacial acetic acid has been compared with perchloric acid as a titrant in 4 solvent systems: glacial acetic acid, acetic anhydride, a mixture of both, and acetone. The comparison was limited to the determination of halides of nitrogenous bases with and without the use of mercury(II) acetate reagent. The results of the visual titrations showed that both acids are comparable tit rants. However, trifluoromethyl sulfonic acid proved to be superior to perchloric acid in potentiometric titrations carried out in acetic acid-acetic anhydride mixtures. Moreover, the nonoxidizing properties exhibited by trifluoromethyl sulfonic acid proved advantageous over perchloric acid in the visual detection of end points in the titration of phenothiazine derivatives in anhydrous acetic acid, using crystal violet indicator.

The ointment bases Lanolinum, Lanae alcoholum unguentum, Zinci unguentum, Polyethylenglycoli unguentum, Unguentum leniens and Unguentum emulsificans, and the emulsifying agents Glyceroli monostearas, Polyethylenglycoli 400 stearas and Polysorbatum 20, 60, 80 were identified by HPTLC and their most important components were determined quantitatively by application of HPLC. The proposed methods of identification are more specific than those described in the monographs of the pharmacopoeias. The obtained results were compared with the nominal values listed in both pharmacopoeias as assays of these bases and emulsifiers are not mentioned, except for glyceroli monostearas.