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H T Karnes

Publications and source records attributed to H T Karnes.

At least 55 records · Page 3Linked to original sources
PubMed1989

High-performance liquid chromatographic method for the determination of salicylic acid and its metabolites in urine by direct injection.

A direct injection method has been developed for the determination of salicylic acid and its metabolites in urine. Urine samples are treated with hydroxylamine to convert salicyl acyl glucuronide to salicylhydroxamic acid, which can be accurately quantitated by direct injection into a high-performance liquid chromatographic system along with salicylic acid, gentisic acid and salicyluric acid. Salicyl phenolic glucuronide is quantitated by difference after hydrochloric acid hydrolysis at 65 degrees C with no loss of salicylic acid by sublimation or hydrolytic loss of salicyluric acid. This method has been applied to urine samples from human subjects and the results are discussed.

Chromatography, High Pressure Liquid↗
PubMed1989

Cardiovascular effects of H2-receptor antagonists.

The type II histamine receptor antagonists, cimetidine and ranitidine, widely used in treatment of peptic ulcer disease have been reported to cause bradycardia. To evaluate the cardiovascular effects of H2 antagonists nineteen healthy volunteers were entered into a double-blind crossover comparison of cimetidine 300 mg qid, ranitidine 150 mg bid, and placebo. Subjects ingested study medicine for 7 days prior to being tested by the Bruce Exercise Test. Heart rate, blood pressure, oxygen consumption, expiratory volume, and fractional expiration of CO2 and O2 were measured at rest, exercise and recovery. A plasma sample for determination of cimetidine and ranitidine levels were obtained prior to the exercise period. Multivariate analysis and paired t test revealed no significant differences for the cardiovascular or pulmonary variables. However, in 5 subjects, the heart rate at 25% maximum VO2 was depressed 8% (P less than or equal to 0.03). This effect in a small percentage of the population suggests that further studies are needed to determine if subpopulations are affected.

Adult↗
PubMed1989

The effects of storage and shaking on the settling properties of phenytoin suspension.

Phenytoin suspension (PHY-S) is reported to settle, resulting in uneven drug distribution and variable patient dosing. We designed this study to determine the rate of settling and the amount of agitation needed to resuspend the preparation. To determine the rate of settling, we thoroughly shook three bottles of PHY-S and then left them undisturbed. We took samples from the top and bottom of each bottle with a microsyringe at 15 minutes, 1, 6, 12, 24, 48, and 72 hours, and 1, 2, 3, 4, and 5 weeks. We simulated patient administration with daily doses that were measured under good, fair, and poor shaking techniques. We analyzed samples after every tenth dose. After complete resuspension the active ingredient in PHY-S settles at a very slow rate. We found no differences in concentration between the top and bottom until the fifth week in the bottles thoroughly shaken and left undisturbed. Minimal agitation is required to resuspend PHY-S. The well-shaken and poorly shaken bottles in the patient simulation phase exhibited no differences in concentrations whereas the unshaken bottle had differences throughout the study period. Problems thought to be associated with PHY-S may be related to compliance and inaccurate measuring devices.

Drug Storage↗
PubMed1989

Recovery of warfarin from an enteral nutrient formula.

The in vitro recovery of warfarin from an enteral nutrient formula after filtration to remove the protein-bound fractions was determined. This study was conducted in two parts. In part 1, 0.25-, 0.50-, and 1-mL aliquots of warfarin sodium stock solution were added to 150 mL of the enteral nutrient formula Osmolite under physiologic conditions to produce warfarin concentrations of 16.7, 33.3, and 66.7 micrograms/mL. In part 2, a 0.5-mL aliquot of the warfarin sodium stock solution was added to Osmolite 100 mL-distilled water 50 mL, Osmolite 75 mL-distilled water 75 mL, and Osmolite 150 mL. The samples were filtered through a membrane that retained macromolecules while allowing warfarin to pass through, and the warfarin concentration was measured by high-performance liquid chromatography. Assays of protein-free buffered control solutions of warfarin before and after filtration indicated that no significant amount of warfarin was retained in the filtration membrane. Significantly less warfarin was recovered from full-strength Osmolite after filtering than before filtering at all warfarin concentrations tested. Significantly more warfarin was recovered from the Osmolite-distilled water solutions than from the undiluted Osmolite. These results suggest that there is some sequestering of warfarin in the macromolecular fraction of the enteral nutrient formula. The decreased recovery of warfarin from the enteral nutrient formula used in this study has potential clinical importance, but further research in humans is needed to substantiate these in vitro observations.

Chromatography, High Pressure Liquid↗
PubMed1989

Concentration uniformity of extemporaneously prepared ranitidine suspension.

The concentration uniformity of an extemporaneously prepared ranitidine suspension was studied. To prepare the ranitidine suspension, 36 150-mg tablets were pulverized and suspended in 180 mL of distilled water. This mixture was diluted with simple syrup to a total volume of 360 mL, resulting in a final ranitidine concentration of 150 mg/10 mL. Samples from each of three bottles that had been filled with 60 mL of the suspension were assayed for ranitidine content by high-performance liquid chromatography. The sedimentation of suspended ranitidine tablet particles was studied by visual observation of the setting process in 10-mL samples from the same batch. The overall mean concentrations (in milligrams per milliliter) of ranitidine were 14.53, 15.25, 13.92, 12.67, and 12.72 at 0, 3, 7, 14, and 21 days, respectively. Compared with baseline, the difference in the ranitidine concentration was not significant over days 0-7. The ranitidine concentration was significantly reduced during the following time intervals: days 0-14, days 0-21, and days 7-21. In the settling experiments, the mean time (+/- S.D.) for sediment to first appear on the test tube bottom was 14.67 +/- 5.35 seconds. Approximately 40-50% (mean level = 3.2 mm) of the total sedimentation level (mean level = 7.3 mm) was observed one minute after shaking. The uniformity of ranitidine suspensions compounded according to procedures described in this report possibly could be improved with sonication. The ranitidine suspension should be well shaken, the dosage should be measured immediately after shaking, and the suspension should be used within seven days of compounding.

Chemistry, Pharmaceutical↗
PubMed1989

Stability of carbamazepine suspension after repackaging into four types of single-dose containers.

The stability of carbamazepine in commercially available suspension that had been repackaged in various single-dose containers was studied. Carbamazepine suspension was repackaged in 2-mL and 8-mL aliquots in amber glass vials, polypropylene vials, and amber polypropylene syringes and in 2-mL aliquots in amber glass oral syringes. Containers were stored at room temperature and continuously exposed to fluorescent light for up to 12 weeks. Samples from each container type and volume were assayed for carbamazepine content by high-performance liquid chromatography at various intervals during storage. Carbamazepine concentrations in the samples were compared with the carbamazepine concentration in the original manufacturer's container. The pH of the samples was also determined, and the suspensions were inspected for color, odor, and large particles. There was no significant decrease in carbamazepine concentration of more than 10% in samples stored for up to eight weeks. After 12 weeks, significant decreases in concentration were observed in all but one container type. No changes in color, odor, or consistency were observed during the 12 weeks, and there were no significant changes in pH. In commercially available suspension repackaged in volumes corresponding to common pediatric doses, carbamazepine (20 mg/mL) is stable for at least eight weeks when stored at room temperature in the containers tested.

Carbamazepine↗
PubMed1988

Ranitidine accumulation in patients undergoing chronic hemodialysis.

Ranitidine accumulation was assessed in 20 patients undergoing chronic hemodialysis following oral daily doses of 150 mg ranitidine for 10 days. Serum ranitidine concentrations prior to dialysis were 191 +/- 115 mcg/l and 207 +/- 172 mcg/l for patients dialyzed three and two times per week, respectively. The amount of ranitidine recovered in the dialysate during the final dialysis session of the study was negligible and ranged from 308-3036 mcg, representing less than 3% of the administered dose. Clearance by hemodialysis was 3.0 +/- 1.1 l/hr. Once daily dosing of 150 mg ranitidine does not result in excessive accumulation, and drug loss during hemodialysis is small. These data suggest that supplemental dosing after hemodialysis is not indicated.

Adult↗
PubMed1987

Automated solid-phase extraction and high-performance liquid chromatographic determination of ranitidine from urine, plasma and peritoneal dialysate.

Ranitidine is an H2-receptor antagonist primarily used to treat peptic ulcer. The present automated solid-phase extraction technique involves sorbent conditioning of a cyano (CN) cartridge with 0.5 ml of methanol and 1.0 ml of extraction buffer (0.005 M phosphate, pH 9). Plasma samples were applied by passing 1.0 ml of plasma through the cartridge and subsequently washing with 2 ml of the extraction buffer. Appropriate larger volumes of dialysate were used to concentrate ranitidine onto the cartridge so that the amount eluted was increased to within detectable limits. Urine samples were deluted with distilled water to decrease the ranitidine concentration to within the range of the standard curve. The high-performance liquid chromatographic method (mobile phase 88-89% of 0.02 M phosphate buffer pH 3 and 11-12% of methanol; Spherisorb phenyl cartridge column, 10 cm X 0.46 cm I.D., 5 micron particle diameter, flow-rate 1.1 ml/min; detection at 228 nm) is sensitive to 2 ng/ml in 1 ml of sample. The internal standard of choice was determined to be n-propionylprocainamide as compared to cimetidine and lidocaine. The method was cost-efficient, rapid and simple due to the automated sample processing. The coefficient of variation on replicate assays was less than 10% over all concentrations studied. Recoveries were between 97 and 110%, and the method was linear over the range 1.90-687.20 with a mean correlation coefficient of 0.999.

Autoanalysis↗
PubMed1987

Enantiomeric resolution of drug compounds by liquid chromatography.

Novel techniques have recently emerged to separate chiral drug compounds into pure enantiomers. The mechanism, experimental difficulties, and applicability of these methods can very greatly, and the choices involved are not straightforward. The most significant new advances in the field of chiral separations have come from work done with liquid chromatographic systems and chiral stationary-phase columns. This review describes several commonly used approaches to chiral separation, dia-stereomeric derivatization, chiral mobile-phase additives, and three major types of chiral stationary phases. Although no single method can be judged superior for every drug application, it appears that chiral stationary phases have received the most attention recently and they are emphasized here.

Chromatography, High Pressure Liquid↗
PubMed1987

Benzyl alcohol interference from heparin lock flush solutions in a high pressure liquid chromatographic procedure for mezlocillin.

During the course of a pharmacokinetic study of the antibiotic mezlocillin, we observed an interfering peak in the high pressure liquid chromatographic analytical procedure that was identified as benzyl alcohol. The benzyl alcohol interferent was traced to a preservative in heparin and saline solutions used to flush heparin locks and indicated that the heparin lock purge volume was inadequate to clean the flushing solution. The present study uses this as a model to study the amount of dilution and contamination interference observed in a controlled study where the purge volume was varied for two "real situation" concentrations of benzyl alcohol in the flush solution. It was found that only 0.5 ml of purge must be drawn to avoid significant contamination interference if benzyl alcohol-free saline is used for dilutions. Contamination interference from benzyl alcohol can also be avoided by spectroscopic or chromatographic resolution if the interference is identified and the particular analyte in question can be resolved. The results of this study provide valuable information for any study in which heparin locks are used and especially in procedures where benzyl alcohol may interfere with the method of analysis. If saline containing benzyl alcohol is used for the dilution of heparin solutions, 1.0 ml of purge must be drawn.

Benzyl Alcohol↗
PubMed1986

Comparative pharmacokinetics of two multiple-dose mezlocillin regimens in normal volunteers.

Mezlocillin was previously reported to exhibit dose-dependent pharmacokinetics. These reports suggest that it may be possible to administer a relatively large dose at a longer interval than is usual and still achieve therapeutic concentrations in serum. In a randomized, crossover study, we compared concentrations of mezlocillin in serum after a single dose and at steady state in 12 healthy volunteers who received 4 g every 6 h and 5 g every 8 h. A slight, but statistically significant, dose-dependent effect was observed upon the area under the concentration-time curve and total body clearance. No accumulation was observed with either schedule. Although concentrations in serum were higher after the 5-g dose, the more frequent administration of the 4-g dose schedule produced serum concentrations above the MIC for susceptible bacteria for a greater portion of the day. In the absence of clear guidelines from human studies which relate serum concentrations to clinical response, the available data indicate that the more frequent dosage schedule is appropriate for severe infections.

Adult↗
PubMed1985

Analysis of N-benzoyl-L-tyrosyl-p-aminobenzoic acid (bentiromide) metabolites in urine by ion-pair high-performance liquid chromatography.

A high-performance liquid chromatographic method is described for the analysis of bentiromide metabolites in urine. The procedure involves no more than direct injection of the diluted urine sample, obviating the need for an extraction step or an internal standard. A mu Bondapak C18 column is used with a mobile phase of 0.01 M tetrabutylammonium chloride (pH 7.4)--methanol (9:1). A flow-rate of 1.4 ml/min, detection at 254 nm and column temperature of 40 degrees C are employed. These conditions were achieved by investigating the effects of mobile phase pH, and concentrations and types of organic modifiers, buffers and ion-pairing agents on the resolution of the metabolites. The analysis time is 18 min per sample and the coefficient of variation on replicate assays is less than 10% for most concentrations studied. Analytical recoveries were between 95 and 100% throughout the appropriate concentration ranges and no interferences were obtained with the exception of p-acetamidobenzoyl glucuronide which could be eliminated by treatment of the samples with beta-glucuronidase. Concentration profiles of the metabolites were studied in normal subjects, and the method was found to be potentially useful for clinical situations in which the existing bentiromide test leads to ambiguous results because of small bowel and hepatic dysfunctions.

4-Aminobenzoic Acid↗
PubMed1985

Evaluation of fluorescence polarization immunoassay for quantitation of serum salicylates.

A fluorescence polarization immunoassay (FPIA) for serum salicylates that has been developed for use with the Abbott TDx analyzer is evaluated with regard to precision, accuracy, and stability of the standard curve. The FPIA method is also compared with a well-established high performance liquid chromatography (HPLC) technique in a clinical laboratory environment. The FPIA demonstrates excellent precision, and the standard curve is sufficiently stable to perform reproducible measurements over a 29-day period without recalibration. Superior accuracy of the FPIA method is indicated for salicylate concentrations between 50 and 800 micrograms/ml by recovery studies and by favorable comparison with the reference method. The performance of the FPIA for salicylate concentrations between 0 and 50 micrograms/ml is somewhat less favorable and should be used with caution in this range. The present method is more appropriate than HPLC for the management of patients receiving chronic high doses of salicylates or in cases of acute salicylate overdose and is also more rapid.

Chromatography, High Pressure Liquid↗