Biomedical subjects
Publications and source records attributed to L L Ng.
Many drugs interfere with the assay of urinary 17-oxo and oxogenic steroids. Some propionic acid derivatives, in particular, tiaprofenic acid, have now been shown to affect this assay. Care should be taken when interpreting results in patients on these drugs.
The metabolism of furaltadone was examined by an in vitro hepatic study in cows and goats and an in vivo study in goats using 14C-labeled and unlabeled drug. The half-life of furaltadone was 13 min in the homogenates of caprine and bovine liver and 35 min in the in vivo study of the goat. Less than 2% of the parent drug was present in the urine of animals dosed either intravenously or intramammarily. No furaltadone was detected in the milk after 24 h. Overall, the parent compound was rapidly absorbed, distributed, and widely degraded in the lactating goat. The compound, labeled at the 2-formyl carbon of the furan ring, had a radioactivity recovery of 81% in the feces and urine. Of the total radioactivity, 99.4% infused into the udder had been absorbed after 72 h. Tissue distributions of radioactivity in decreasing order of abundance were: kidney, udder, liver, duodenum, muscular tissue, adipose tissue, and bile.
A quantitative clean-up procedure for drugs in plasma and urine in preparation for high-performance liquid chromatographic analysis is discussed. Samples are mixed with zinc sulfate, barium hydroxide, and acetonitrile (or methanol). Resultant solutions are clear and free of visible residue. Injections of over 420 samples of treated urine and 120 samples of treated plasma had no noticeable effect on pressure drop and column performance. An examination of the column head indicated no damage or discoloration to the packing. Baselines of the controls show no interference from endogenous compounds for the drugs studied. Precision study using cyclobenzeprine . HCl in plasma and urine by internal standard and external standard methods has within-run and day-to-day variations of under 5%. Drugs studied in urine and plasma are amiloride . HCl, cyclobenzeprine . HCl, cyproheptadine . HCl, diflunisal, indomethacin, phenylbutazone and sulindac. These drugs are selected for the various functional groups, their binding by proteins and their natural UV absorptivity. Conditions to improve recovery, advantages and limitations are discussed.
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The juice of the banana trunk produces a non-depolarising neuromuscular block. Oxygenation of the extract enhances its potency. Reversals with anticholinesterases are transient. Partial reversals in isolated preparations indicate these could be both specific and non-specific binding which could account for blockade after washing. It could be specifically bound to ACh receptors in an irreversible way since its action appears similar to that of alpha-BuTX.
Several previous investigations have suggested that there may be different growth hormone isoforms in patients with acromegaly. We used three different site-specific monoclonal antibodies (MAbs) to investigate growth hormone (GH) isoforms in serum from an 8 year-old girl with a GH and prolactin secreting adenoma. The pattern of GH-immunoreactivity was dependent on the circumstances of collection. Serum obtained after oral glucose had very little cross reactivity with MAb 352 although concentrations of up to 15 micrograms/l were found with two other MAbs, 033 and 665. MAb 352 does not recognize the 20,000 dalton isoform of GH (20K) while both MAb 033 and 665 do. The same pattern of GH immunoreactivity (low MAb 352, equal and higher MAb 033 and 665) was seen in other baseline samples. In contrast, samples obtained after TRH/GnRH showed immunoreactivity patterns expected for a mixture of 22,000 dalton isoform of GH (22K) with only a small amount of 20K. GH samples obtained during sleep showed both patterns with episodic peaks with equal immunoreactivity superimposed on the basal pattern (decreased activity with MAb 352). Affinity chromatography of basal samples showed that a portion of the GH immunoreactivity was neither 22K nor 20K, although in stimulated samples, over 70% of GH was 22K or 20K GH. In conclusion, the nature of GH isoforms present in serum varies with GH concentration. These differences may contribute to the known difficulty in correlating disease activity and random GH measurements in patients with GH secreting adenomas.
A reverse-phase liquid chromatographic method for determination of dexamethasone acetate and of cortisone acetate was subjected to an interlaboratory study by 8 collaborators for each steroid acetate. Bulk drug substance, suspensions, and tablets were assayed. Bulk drug or dosage form is dissolved in an acetonitrile-buffer mixture and analyzed by an external standard method. The steroid acetate is resolved from extraneous components by reverse-phase chromatography and detected at 254 nm. The sample solutions are stable for at least 72 h. For dexamethasone acetate, coefficients of variation were 0.9 and less than or equal to 3.1% for the bulk drug substance and the suspensions, respectively. For cortisone acetate, coefficients of variation were 0.7% for bulk material, less than or equal to 2.0% for suspensions, and less than or equal to 2.5% for tablets. All dosage forms were commercial formulations. The 2 methods have been adopted official first action.
This study, presented as a technical communication, describes a reversed-phase liquid chromatographic method for select commercial formulations, namely, inhalation solution, nasal solution, capsule and inhalation aerosol. Miscellaneous validation parameters are also discussed.