An ORS-ICP-MS method for monitoring trace levels of cobalt and chromium in whole blood samples from hip arthroplasty patients with metal-on-metal prostheses.

OBJECTIVE: To develop a rapid and reliable method, using an octopole reaction system (ORS) ICP-MS, capable of monitoring trace levels of Co and Cr in whole blood samples from hip arthroplasty patients with metal-on-metal prostheses. DESIGN AND METHOD: Whole blood is diluted 10-fold with an alkaline diluent and analyzed using an Agilent 7500 CE ORS-ICP-MS. RESULTS: Limit of quantification of 0.03 µg/L Co and 0.20 µg/L Cr in patient samples. <6% covariance obtained for quality control materials analyzed over 10 runs. CONCLUSION: This method is capable of monitoring trace levels of Co and Cr in diluted whole blood samples with a vial to vial run time of approximately 2 min. Results are comparable to those obtained using high resolution (HR) ICP-MS with sample digestion.

Laboratory restructuring in metropolitan Edmonton: a model for laboratory reorganization in Canada.

In 1994 the Alberta government acted to reduce to a decade-long deficit in the provincial budget with draconian reductions in the health, education and welfare expenditures. As a result, funding to Alberta clinical laboratories was to be reduced by approximately 40%. In response, the private and public laboratories in metropolitan Edmonton formed a unique alliance to provide laboratory testing in a more coordinated and efficient manner. Of the five metropolitan hospitals, only University of Alberta Hospital preserved its full service laboratory and its specialty reference testing. The other hospital laboratories were converted to rapid response laboratories with a merged private reference laboratory providing routine testing and support to the four hospitals, and far fewer outpatient collection facilities. This paper describes the steps in the laboratory restructuring from inception to execution.

Evaluation of a kinetic assay for angiotensin converting enzyme.

We have verified the analytical reliability of a Sigma reagent kit, which is a modified method of Holmquist et al. (1) for the determination of angiotensin-converting enzyme (ACE) on the Abbott ABA-100 analyzer. The reaction was linear up to 160 U/L. Correlation with a radiometric method (Ventrex Laboratories) was good except for a negative constant bias and loss of linearity with the radiometric method at high levels. The reconstituted reagent was determined by atomic absorption spectroscopy to contain 5.6 mumol/L of zinc. An increase in zinc content up to 45.6 mumol/L had little or no effect on enzyme activities of preparations from three mammalian species: rabbit, guinea pig and human. Neither was ACE activity inhibited by preincubating each of two serum pools with any of four corticosteroids for up to 8 d. Enzyme activity in samples remained stable at 5 degrees C for 8 d.

Evaluation of an ultrafiltration-fluorescence polarization immunoassay for monitoring unbound phenytoin.

To evaluate a new ultrafiltration-fluorescence polarization immunoassay (FPIA) for monitoring blood levels of unbound phenytoin, the drug, with or without a 14C label, was added to three serum pools obtained from normal, uremic, and hypoalbuminemic patients and to 10 individual patient sera that varied greatly in phenytoin binding (11-50%). Protein-unbound phenytoin fractions were obtained from the sera by ultrafiltration using the Amicon Micropartition System and by a classic equilibrium dialysis method. The percent unbound phenytoin in each serum was determined by a radioassay and an automated FPIA (TDx System). An analysis of variance revealed no significant difference in the percent unbound phenytoin obtained at 37 degrees C by the FPIA and radioassay methods (alpha = 0.05). The data indicate that the ultrafiltration system can be combined with FPIA to produce a convenient laboratory method for routine therapeutic drug monitoring that gives results comparable to the equilibrium dialysis, radioassay reference method.

An evaluation of common methods for acetaminophen quantitation for small hospitals.

Rapid, reliable serum acetaminophen quantitations assist in the diagnosis of the toxic patient and direct the clinician in the course of aggressive treatment. Reliable performance must be tempered with economic consideration, especially for small laboratories with infrequent testing. Two commonly available colorimetric techniques for acetaminophen (nitration and ferric reduction) are evaluated using both commercial and laboratory reagents. Enzyme immunoassay (EMIT) is also performed. Results are compared to an HPLC reference method.

Factors affecting the analysis of cefoperazone in cerebral spinal fluid.

The measurement of cefoperazone concentrations in cerebral spinal fluid (CSF) is important to understanding the biodisposition and pharmacokinetic behavior of the drug. We have demonstrated that cefoperazone is unstable in methanol and at alkaline pH and these factors may affect the accurate quantitation of the drug in CSF. Buffering CSF samples with acetate is recommended to improve cefoperazone stability in CSF.

Isolation of peptides from uremic plasma that inhibit phenytoin binding to normal plasma proteins.

The binding of many drugs to plasma proteins is altered in renal disease. Explanations include hypoproteinemia, alterations in the native structure of the binding protein, and competitive or noncompetitive inhibition. The binding of phenytoin to proteins was studied in plasma from patients with chronic renal failure by equilibrium dialysis at 37 degrees. Charcoal adsorption was used to normalize the binding. Substances that appeared to be peptides were isolated; they inhibited the binding of phenytoin to normal plasma proteins. The data suggest that the defect in phenytoin-protein binding in chronic renal failure may be due to competitive or noncompetitive inhibition by peptides.

Phenytoin binding to partially purified albumin in renal disease.

Drug binding to protein is known to be altered in renal disease. Explanations include hypoproteinemia, competitive or noncompetitive inhibition, and basic functional defects in the binding protein. Albumin, the primary binding protein for phenytoin (DPH), was isolated from the plasma of patients with severe renal failure as well as from normal controls. DPH binding was not different between the albumin preparations isolated from the two sources, although some differences were detected in the apparent affinity constant and the number of binding sites. It would appear that the significant defect in DPH binding in renal disease cannot be attributed to a basic functional defect in the drug-binding protein albumin.

Determination of plasma octopamine and its level in renal disease.

A radioenzymatic assay method for the estimation of octopamine levels in plasma was developed. Preparation of the enzyme, phenylethanolamine-N-methyl transferase, dilution of the plasma sample, preparation of a suitable blank, and the assay conditions were found to have a significant effect on the sensitivity of the assay. Plasma octopamine levels were measured in a population of 33 normal individuals ranging in age from 19 to 94 years. Significantly higher plasma octopamine levels were found in the age group 70-90 years. Excluding those individuals over the age of 70 years, no significant differences in plasma octopamine levels were found for males or females, the range of values was 0 to 0.68 ng per ml, with a mean value of 0.23 ng per ml (n = 25). Examination of plasma octopamine levels in patients with severe renal disease requiring hemoperfusion dialysis, revealed a significantly higher level of plasma octopamine in renal disease (1.9 ng per ml), and an increase in plasma octopamine during dialysis; the mean level post dialysis being 2.7 ng per ml.