An analytical method has been developed for the determination of a new antiepileptic drug, CGS 18416A, in human plasma. CGS 18416A is a new anticonvulsant representative of a novel class of water-soluble agents being developed for the treatment of epilepsy. Preclinical trials indicate sustained efficacy at relatively low oral doses, indicating a need for a sensitive assay. The method is based on capillary gas chromatography/mass spectrometry and utilizes stable isotope-labelled CGS 18416A as the internal standard. Samples (1 mL) are acidified, then washed with pentane/ethyl acetate, followed by liquid/liquid extraction at pH 11 with pentane/ethyl acetate. Extracts are then concentrated and analysed directly by gas chromatography/mass spectrometry. Separation is accomplished on a thick film methylsilicone capillary column. Mass spectrometry was carried out under positive ion ammonia Cl conditions with selected ion monitoring of the protonated molecular ions (m/z = 248 and 252) for CGS 18416A and the 13CD3-CGS 18416A, respectively. Specificity was demonstrated by the lack of interfering peaks at the retention time of CGS 18416A and the internal standard. Recovery and reproducibility assessments indicate good accuracy and precision over the validated concentration range of 0.2-51 ng/mL. The limit of quantification is 0.2 ng/mL and the method has sufficient sensitivity to support clinical trials. This is illustrated with an example of quantification in a normal volunteer following oral dosing.

Anticonvulsants↗

PubMedDate not supplied

Quantitative determination of CGS 18102A, a new anxiolytic, in human plasma using capillary gas chromatography/mass spectrometry.

CGS 18102A is a novel hexahydrobenzopyranopyridine that has a mixed pharmacological profile of 5-HT-1A agonist and 5-HT-2 antagonist properties. Based upon these mechanisms, the compound is predicted to have anxiolytic efficacy with possible efficacy in depression. Preclinical studies in the rat have shown the drug to be well absorbed and extensively metabolized. Because of the anticipated low plasma levels in humans a gas chromatography/mass spectrometry (GC/MS) analytical method has been developed and validated to determine plasma concentrations of CGS 18102A in early clinical studies. The method utilizes CGS 18416A as the internal standard. Samples (1 mL) were extracted with pentane:ethyl acetate (75:25, v:v). Extracts were then concentrated and analysed directly by GC/MS. Separation was accomplished on a methylsilicone capillary column (30 m x 0.32 mm i.d.). GC/MS was carried out under positive ion ammonia CI conditions, with selected ion monitoring of the [M + H]+ ions (m/z = 262 and 248) for CGS 18102A and CGS 18416A, respectively. The method was successively applied to the analysis of clinical samples from an ascending multidose safety and tolerability study conducted in six normal healthy male volunteers.

Adolescent↗

PubMedDate not supplied

A method to obtain maternal-fetal plasma samples using a microsampling technique in the rat: transplacental passage of cefoxitin.

A microsampling technique that allows taking blood samples from the umbilical vein of the pregnant rat is described. Such techniques are needed in order to allow pharmacokinetic and embryo exposure to be correlated with teratogenic endpoints. Cefoxitin was administered intravenously (300 mg/kg) into tracheotomized, pentobarbital anesthetized dams on day 21 in gestation. Blood samples were collected via the carotid artery from the dam and the umbilical vein of the fetus at designated times. Up to three samples of 20 to 30 microliters each, were taken from individual fetuses at 20-min intervals. With few exceptions, fetal cefoxitin concentrations were homogeneous at each sampling period. Fetal concentrations were low compared to maternal concentrations as seen by the small fetal/maternal area under the curve ratio (0.053 +/- 0.006).

Animals↗

PubMedDate not supplied

[Chronic hepatitis C in patients coinfected by human immunodeficiency virus].

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Anti-HIV Agents↗

PubMedDate not supplied

Antibodies to the AIDS-associated retrovirus in hemophiliacs and other individuals from southern Spain: lack of correlation with lymphocytes sub-populations.

Exposure to the AIDS-associated retrovirus (ARV) has been observed in 54 hemophiliacs in Southern Spain who have received commercial coagulation factors manufactured in the United States. Contact with ARV could be detected in some sera collected in 1982. Frequency among asymptomatic hemophiliacs was 44%, in individuals with lymphadenopathy syndrome 71%, and 2 AIDS cases were seropositive. Evidence for exposure to ARV did not correlate with changes in the lymphocyte populations or in the clinical condition of the patients. Only the amount of factor received distinguished the seropositive and the seronegative groups of hemophiliacs. Exposure to ARV was also detected in sera from homosexual men and I.V. drug addicts. The results indicate that members of AIDS risk groups in Spain have had contact with the AIDS retrovirus.

Antibodies, Viral↗

PubMedDate not supplied

[Calcification and contamination as complications in the use of double-J catheters: incidence and correlation].

We present a series of cases of complex renal lithiasis, in which we carried out temporary internal urinary bypassing, prior to extracorporeal lithotripsy, by means of the retrograde insertion of a double-J urethral catheter, studying the time of stay, the presence or not of contamination in the catheter and its relationship with the calcifications found in them. We also carried out a metabolic-functional study of each patient, determining the urinary pH and the serum and urinary calcium, phosphorous and uric acid concentrations, and observing their possible influence on the above-mentioned complications. Of the 25 catheters studied, we observed calcification in 11 cases (44%). In these we observed urealytic germs (Proteus and Pseudomonas), without finding modifications of urinary pH. We observed no relationship between the calcium deposits and serum and urinary calcium, phosphorous and uric acid concentration.

Adult↗