Capillary gas chromatographic determination of spermidine in diet integrators.

Biogenic polyamines, among which is spermidine (SPD, NH2-(CH2)4-NH-(CH2)3-NH2), are ubiquitous polycationic molecules that have a definitive role in many biological processes, such as nucleic acid metabolism, protein synthesis and cell growth. SPD is present in diet integrators because it seems to favour the hair growth. This work describes a capillary gas chromatographic (CGC) method for the quantitative determination of SPD in diet integrators using cadaverine internal standard (IS), a methyl siliconic capillary column and flame-ionization detector (FID). Diet tablets, containing SPD, are pulverized; an aliquot of powder is treated with an alkaline aqueous solution and added with IS. The suspension is extracted with diethyl ether containing ethyl chloroformate (ECF). The ether extracts, evaporated to dryness and reconstituted in ethyl acetate were analyzed in CGC/FID. Derivatives of polyamines with ECF were characterized in CGC/MS too. Validation has considered specificity, linearity, precision and accuracy of analytical method; this parameters are valid for the quantitative determination of SPD in diet integrators.

Flash alkylation for the identification of barbiturates in biological material.

The gas chromatographic identification of barbiturates isolated from biological material is not optimal, and due to their polar nature, it is difficult to obtain good resolution on most columns. To improve resolution, flash alkylation appeared to be a reasonable alternative. Methyl, ethyl, and butyl derivatives were prepared for various drugs found in the "acid-neutral" extract and the Kovats retention indices (Ir) were determined on SE-30, OV-17, and SP-2250. The Ir of the alkylated derivatives of the barbiturates are highly reproducible. One column and two alkylated derivatives can be used for the qualitative analysis of barbiturates in extracts of biological material, even when the Stas-Otto extract is used.

Use of the retention index in gas chromatographic studies of drugs.

In earlier studies, it has been shown that the retention index (Ir) is a very reproducible measure of gas chromatographic mobility. Statistically comparing Ir values obtained here with those found in references has yielded very satisfying results. This will enable the use of Ir values in the screening phase of analysis for general unknowns using the great number of data offered by references; thus limiting the range of inquiry to no more than 6 or 7 drugs, provided that the unknown is between the scheduled ones. An index of analytical behavior that is an absolutely reproducible number will be necessary for computerizing toxicological analysis.

[Use of RIA (radioimmunoassay) technics in the identification of narcotics in biological fluids]. / Applicazione delle tecniche "R.I.A." alla identificazione di sostanze stupefacenti in liquidi biologici

Radioimmunoassay has been compared with extraction thin-layer chromatography and gas-chromatography for the detection of morphine and barbiturate in urine. Radioimmunoassay has been found to be the most sensitive and rapid method and its use in large scale screening and forensic toxicology is considered.

[Chemical-toxicological diagnosis in 16 cases of "intravenous narcotism" deaths (author's transl)]. / La diagnosi chimico-tossicologica nelle morti da morfinici: considerazioni su 16 casi.

The chemical-toxicological diagnosis aspects involved in 16 cases of "intravenous narcotism" deaths are discussed. Liquids and biological materials were directly tested by RIA, GLC and TLC. According to the Authors, RIA is assumed to be more speedy and more sensitive than traditional chemical technics. Therefore RIA is proposed for quantitative determination of morfina and its derivates in biological liquids and viscera, previous the qualitative confirmation by the chemical tests.

Cannabinoid-free Cannabis sativa L. grown in the Po valley: evaluation of fatty acid profile, antioxidant capacity and metabolic content.

Within a project aimed to reintroduce non-drug hemp cultivars in the Italian Po valley, for fibre but also high added-value nutraceutical production, investigation on locally grown plants has been performed, in order to assess their oil and metabolic content. This study provides useful information regarding three different hemp cultivars, from two sites, in view of their potential industrial application. The oil was characterised by a high unsaturated/saturated fatty acid ratio and by an almost perfect balance of ω-3 and ω-6 fatty acids, as requested for healthy foods. The alcoholic extracts, for which a high content of amino acids and phenolic compounds has been highlighted, could provide dietary supplements to help in preventing oxidative stress. By investigating the Carmagnola cultivar, six known and four new lignanamides have been identified, confirming and assessing the general metabolic pattern in the seeds of these locally grown plants.

Preliminary gas chromatography with mass spectrometry determination of 3,5-dimethoxyphenol in biological specimens as evidence of taxus poisoning.

Taxus baccata is a widely distributed yew often associated with cases of fatal intoxication, which is related to the high amounts of cardiotoxic alkaloids, taxine A and taxine B, contained in its leaves. In this paper, a case of Taxus fatal poisoning, hypothesized by the forensic autopsy, has been confirmed by the application of both gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-tandem mass spectrometry (LC-MS-MS) techniques. A GC-MS method was used for the determination of the derivatized 3,5-dimethoxyphenol, a cyanogenic aglylactone considered as a marker of Taxus poisoning, being present in all species of Taxus. The detection by LC-MS-MS of taxine B and isotaxine B in the biological specimens confirmed the absorption of cardiotoxic alkaloids and allowed to established the cause of death as the ingestion of Taxus baccata leaves.

Absorption of oral lornoxicam in healthy volunteers using a granular formulation in comparison with standard tablets.

The bioavailability of lornoxicam (CAS 70374-39-9), a novel highly potent anti-inflammatory and analgesic agent, was studied in healthy volunteers after single doses of a new oral formulation (8 mg granules) in comparison to tablets (8 mg). Eighteen healthy volunteers (6 males and 12 females) with a mean age of 29.4 were given a single 8 mg dose of each formulation in an open, cross-over study, with randomised sequences. Lornoxicam plasma levels were determined by an HPLC method. Cmax, AUC0-infinity and t 1/2 beta values were similar for both the granules and tablets, but tmax and lag time values after lornoxicam granules were significantly shorter than after the tablets. During the study, no side-effects were noted with either of the formulations studied. Therefore this study showed that lornoxicam granular formulation had a faster absorption than tablets even though the two formulations can be considered bioequivalent.

Pharmacodynamics and pharmacokinetics of pinacidil in normotensive volunteers after repeated doses of a new slow-release tablet formulation.

Pinacidil (CAS 85371-64-8) is an antihypertensive drug of the class of agents called "potassium channel openers". The pharmacokinetics of were studied after repeated oral administration of a new slow release tablet formulation (Pindac) as compared with the standard slow release capsule formulation in healthy volunteers. Eighteen healthy volunteers (3 males and 15 females), aged from 22 to 48 years, and 49 to 95 kg in weight, were given a 12.5 mg dose of each formulation every 12 h for 7 days on two occasions, in a randomized, cross-over trial with at least two weeks interval between trials. Blood samples were drawn immediately before drug administration on the morning of days 1, 2, 3, 4, 5, 6, and 7 and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 and 36 h after the last drug administration. Blood pressure, heart rate, and respiratory function were assessed at admission and on the morning of day 0 (baseline), 2 and 7, before drug administration, and at 4, 24 and 36 h after the final administration. Pinacidil plasma levels were determined by an HPLC method. Both formulations elicited similar reductions of systolic and diastolic pressures from 4 h after administration, but did not change heart rate. The main model-independent pharmacokinetic parameters of pinacidil (Cmax, Tmax, AUC, MRT), as well as the absorption and elimination half-lives were similar with the two formulations. During the study there were no complaints of side-effects with either of the formulations. One advantage of the new formulation as compared to the capsules is that the tablets can be cut easily and the dosage adapted to a patient's needs.

Pharmacodynamics and pharmacokinetics of pinacidil after a single dose of a new slow release tablet in healthy volunteers.

Pinacidil (CAS 85371-64-8) is a recently developed antihypertensive drug of the class called "potassium channel openers". It produces vasodilatation and a fall of arterial blood pressure. The pharmacokinetics and the pharmacodynamics of pinacidil were studied after single oral administration of a new slow-release tablet formulation (Pindac) in comparison to the standard slow-release capsule formulation in healthy volunteers. Eighteen healthy subjects (3 men and 15 women), with a mean age of 31.1 years were given a single 12.5 mg dose of each formulation in an open, cross-over study, with randomised sequences and a 7-day wash-out period between doses. Blood samples were collected before and several times up to 36 h after drug administration. Blood pressure, heart rate and respiratory functions were assessed before and 1, 4, 24 and 36 h-after drug administration. Pinacidil plasma levels were determined by HPLC. Both formulations produced a similar significant reduction (10 +/- 4 mmHg) of systolic blood pressure 4 h after administration but no changes of diastolic pressure and heart rate. Both the maximal effect (Emax) and the area under the effect-time curve (AUE0-36) were similar for the two formulations. The main model-independent pharmacokinetic parameters of Pinacidil (Cmax, Tmax, AUC, MRT) as well as the absorption and the elimination half-lives were similar after the two formulations. The main advantage of the tablet formulation compared to the capsules is that tablets can be easily cut and therefore the dosage can be adapted to an individual patient's needs.

Gonadal function in male heroin and methadone addicts.

Gonadal function was elevated in 80 male heroin and/or methadone addicts by measuring basal plasma levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL) and testosterone. In 41 subjects semen analyses were also undertaken. Three groups were distinguished consisting of 15 heroin addicts, 42 undergoing methadone treatment but continuing to take heroin, and 23 taking only methadone. All patients had normal plasma levels of FSH, LH and testosterone. Prolactin levels were normal in all subjects except for the 15 heroin addicts, in whom they were significantly higher than in controls (P less than 0.025). Semen analyses from all of the heroin addicts and from the dual heroin-methadone users were abnormal, whereas only 10 out of 22 (45%) of the methadone takers were pathological. In all cases asthenospermia was one of the abnormalities (100%). Twenty-four per cent also showed teratospermia and hypospermia and 17% showed oligozoospermia. Such seminal pathology, especially of forward motility, even in combination with normal hormone levels, might be an early indication of heroin toxicity to the male reproductive tract.

Polar Constituents of Calceolaria ascendens1.

A new phenylpropanoid glucoside, 1'- O-beta- D-(3,4-dihydroxy-beta-phenyl)-ethyl-4'- O-caffeoyl-beta- D-apiosyl-(1'''-->3')-glucopyranoside, named calceolarioside E, was isolated from CALCEOLARIA ASCENDENS Lind., together with two other phenylpropanoid glucosides, verbascoside and forsythoside A, and cyclohexanols rengyol, isorengyol, and 4-hydroxy-4-(2'-hydroxyethyl)-cyclohexanone.

Pharmacokinetics of two new oral formulations of ibuprofen.

Two new formulations of ibuprofen were studied in 600 mg coated tablets and granules, to allow an easier adjustment of its daily dosage now higher than in the past. Six healthy volunteers (3M and 3F, mean age 32.6 years took part in a 6 X 6 Latin Square single dose pharmacokinetic study comparing six oral formulations of ibuprofen: 600 mg coated tablets, 300, 400 and 600 mg resinated granules, 300 and 400 mg sugar-coated tablets available on the market as Brufen. The results show that there is a correlation between dose and the area under the blood concentration-time curve. The availability of ibuprofen was similar irrespective of whether it is given in the form of granules or in tablets. The short half-life and the widespread use of ibuprofen give an acceptable range of safety to these new formulations.

The pharmacokinetics of clotiazepam after oral and sublingual administration to volunteers.

We have studied the single dose pharmacokinetics of 5 mg clotiazepam drops, oral tablets, and sublingual tablets in a cross-over study in 6 healthy volunteers (median age 28 years). The formulations had similar systemic availability. Compared with oral tablets the sublingual route gave a lower peak concentration and a delayed peak time, while drops gave a greater maximum concentration with a similar peak time. The use of drops is suggested for a more marked initial effect and the sublingual route for easier administration, especially in the elderly.