High-performance liquid chromatographic system for the separation of tricyclic antidepressant and related drugs using ODS-Hypersil.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to R Gill.
Explore the source record for details and available documents.
The reproducibility of the separation of basic drugs on silica columns has been tested in a collaborative study between nine laboratories. The results from the different laboratories were very similar. Various methods of recording the retention properties of the drugs were compared with reference to their reproducibility and ability to discriminate between different compounds. Relative retention times, relative capacity factors, and corrected capacity factors were much better than retention times and capacity factors, although all the methods suffered from large errors with weakly retained compounds. All the work was carried out using a single batch of silica to avoid variations due to the stationary phase.
A method has been developed for the separation of thiazide diuretics and a number of related drugs by high-performance liquid chromatography on an ODS-Hypersil column with acetonitrile-1% aqueous acetic acid as the eluent. The effects caused by changes in the separation conditions on the reproducibility and robustness of alternative methods for recording retentions (including capacity factors, retention indices based on the alkyl aryl ketone scale, and relative capacity factors compared to a thiazide standard) have been examined. The results confirm that good interlaboratory reproducibility will only be achieved when operators control the temperature of the column and use the same brand of column packing material. The retentions should be recorded using a relative method, as these were found to be virtually independent of minor variations in the eluent composition.
Electrophysiological studies using a cortical slice preparation revealed that MK-801 is a potent, non-competitive, antagonist of N-methyl-D-aspartate (NMDA)-induced depolarisations. Also, MK-801 was a highly selective antagonist, exhibiting a high degree of use-dependency. It completely blocked responses to NMDA and quinolinic acid but had no effect on responses produced by kainic acid or quisqualic acid. Using [3H]MK-801, high affinity binding sites for MK-801 were detected in membranes of the rat brain. The pharmacological specificity and regional distribution of binding sites for MK-801 were consistent with an action of the compound at the level of the NMDA receptor-associated ion channel. Administered parenterally, MK-801 had a remarkable neuroprotective role. It caused essentially complete protection against loss of neurones produced by injection of neurotoxic doses of NMDA or quinolinic acid into the striatum or hippocampus. Furthermore, MK-801 was highly effective in preventing loss of hippocampal neurones following bilateral occlusion of the common carotid arteries in the gerbil.
Explore the source record for details and available documents.
While mild to moderate hepatic dysfunction is commonly encountered in infectious mononucleosis induced by Epstein-Barr virus (EBV), clinical jaundice with high bilirubin levels (greater than or equal to 6.0 mg/dL [greater than or equal to 103 mumol/L] is only occasionally encountered. In this study, seven patients with primary EBV infections had peak bilirubin levels of 10.2 to 23.0 mg/dL (174 to 393 mumol/L) and, for the most part, presented initial diagnostic problems. Complications included the virus-associated hemophagocytic syndrome and acute respiratory distress syndrome in one patient and transient renal failure in another. The laboratory data suggested that a combination of hemolysis and viral-induced cholestasis was responsible for the intense hyperbilirubinemia in at least five patients. Physicians should be aware that marked hyperbilirubinemia can occur with EBV-induced infectious mononucleosis and, thereby, obviate the need for costly diagnostic laboratory tests and, occasionally, invasive procedures.
The neuroprotective effects of MK-801, a noncompetitive antagonist of N-methyl-D-aspartate (NMDA) receptors, were evaluated in models of cerebral ischemia using Mongolian gerbils. Bilateral occlusion of the carotid arteries for a period of 5 min resulted in a consistent pattern of degeneration of hippocampal CA1 and CA2 pyramidal neurons, which was quantified using an image analyzer. Systemic administration of MK-801 (0.01-10 mg/kg, i.p.) 1 hr prior to the occlusion caused a dose-dependent protection of the CA1 and CA2 neurons. The ED50 value for neuroprotection by MK-801 was calculated to be 0.3 mg/kg, and at doses greater than or equal to 3 mg/kg the majority of animals were completely protected against the ischemic insult. Systemic administration of MK-801 (1 or 10 mg/kg, i.p.) 1 hr prior to unilateral occlusion of the right carotid artery resulted in significant protection against hippocampal neurodegeneration following 10 min of occlusion, and increased the survival rate after 30 min of occlusion. The potent neuroprotective effects of MK-801 in these cerebral ischemia models add further weight to the evidence that NMDA receptors are involved in the mechanism of ischemia-induced neuronal degeneration.
High-performance liquid chromatography retention data are presented for over 40 analgesic drugs on an ODS-silica packing material to assist in the identification of these compounds. Three isocratic eluents prepared from isopropanol, formic acid and an aqueous phosphate buffer have been used. One eluent has been used for the analysis of paracetamol in whole blood.
The high-performance liquid chromatographic (HPLC) retention characteristics of 21 benzodiazepine drugs and some of their metabolites have been examined on both silica and ODS-silica packing materials. Four HPLC systems have been considered and retention data are presented for the drugs on these systems. The correlation of retention data on the systems is considered with reference to the problem of identifying unknown benzodiazepines.
The separation of the local anaesthetic drugs by reversed-phase high-performance liquid chromatography using a Hypersil ODS column has been examined in order to identify critical factors in the establishment of a retention database for interlaboratory comparisons. An eluent of methanol-aqueous orthophosphoric acid (15:85, v/v) (pH 2.5) containing 0.7% hexylamine has been used. The effects of small changes in the eluent composition, pH, temperature and the use of different column packing materials on the retentions of the analytes have been studied. The use of capacity factors, relative capacity factors and retention indices based on the alkylarylketone scale have been compared.
The potential advantages of using 1-mm bore high-performance liquid chromatography columns to replace conventional 4-5-mm bore columns for routine drug analysis have been considered in the light of various claims and counter-claims in the scientific literature. Experimental work has been conducted to measure the changes in mass sensitivity when using both UV and electrochemical detection. Further work has investigated the coupling of these narrow-bore columns in order to achieve high plate counts with particular reference to the influence of peak asymmetry. Finally the linking of the narrow-bore columns to a mass spectrometer with a moving-belt interface has been examined. All results are discussed with reference to the needs of the routine analyst.
Explore the source record for details and available documents.
The allograft response is a response by host T lymphocytes reacting to transplantation antigens that are carried on allogeneic lymphoreticuler cells. In vivo this response usually leads to graft rejection. It is possible to circumvent this response by the elimination of the lymphoreticular cells from the grafts prior to transplantation. The paradox of the strong response to transplantation antigen on lymphoreticular cells and the weak response to the same antigen on graft parenchymal cells can be explained by the signaling requirements for T lymphocyte activation.
A collaborative study among 10 laboratories has been undertaken to investigate the interlaboratory reproducibility of retention measurements in a high performance liquid chromatographic (HPLC) system for separating barbiturates. The system involved an ODS-Hypersil column with an eluent of methanol:phosphate buffer (40:60, v/v) at pH 8.5; all laboratories used the same batch of packing material. The conventional methods of recording retention properties (retention times and capacity factors) gave poor interlaboratory reproducibility. Better results were obtained by expressing the retentions relative to a standard barbiturate (quinalbarbitone); relative adjusted retention times proved to be more effective than straightforward relative retention times. Retention indices based on the alkylarylketone scale were not as reproducible as the methods based on a single closely related compound. The best reproducibility was obtained using corrected capacity factors based on the retention of four barbiturates in a standard mixture. The results of the study are discussed with a view to selecting the best methods of recording retention in HPLC when considering the establishment of databases for drug identification.
Explore the source record for details and available documents.
Common carotid artery (CCA) blood flow was measured noninvasively with a pulsed Doppler duplex scanner modeled after the Octoson (Ultrasonics, Inc., No. Yonkers, N.Y.). The aim of the study was to determine normal values and to assess the accuracy of CCA flow as a predictor of internal carotid artery (ICA) stenosis. One hundred one people who did not have disease were studied; the overall mean flow rate was 395 +/- 79 ml/min (mean +/- S.D.). There was no significant correlation with age, height, or body surface area but there was with body weight (p less than 0.05). A statistically significant difference was evident between men (424 +/- 88 ml/min) and women (371 +/- 62 ml/min) (p less than 0.001). The intrasessional variation (S.D./mean) was 13% and the intersessional variation, 16%. No significant difference was seen between the sides. Ninety-two patients who had carotid angiography were studied and the flow rates compared with the degree of ICA stenosis on each side. The flow rate for mild ICA stenosis (1% to 39%) was 404 +/- 109 ml/min, for moderate stenoses (40% to 69%), 390 +/- 91 ml/min, and for severe stenoses (70% to 99%), 351 +/- 109 ml/min. There was a significant difference in flows only between mild and severe grades of stenosis of the ICA (p less than 0.01). With unilateral stenosis, comparison of flow values in the normal and affected sides showed the greatest discriminatory power when the absolute difference of flow values was taken (p less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)
This article describes the preliminary findings of a Duplex ultrasound technique that enables the patency of the portal circulation and portosystemic shunt patency to be determined. In addition, the equipment allows the noninvasive measurement of quantitative rates of blood flow in these vessels. Portal vein flow was 952 +/- 273 ml/min in 10 normal subjects after an overnight fast and increased by 50% at 30 minutes in response to a standard 660-calorie liquid meal. Thirteen portosystemic shunts were scanned, and hemodynamic information was obtained from 10. Three of the four patients who had a Warren shunt performed 3 to 4 years earlier had portal vein occlusion. There is evidence of an increase in flow through the Warren shunt on feeding, suggesting a hemodynamic connection to the mesenteric side of the circulation. The apparatus, technique of examination, and the characteristics and difficulties with particular types of shunts are described.
Explore the source record for details and available documents.