The fundamentals of high-performance liquid chromatography (HPLC), as applied in small-scale studies of drug stability, are presented. Chromatography is the separation of a complex mixture into its individual compounds t...The fundamentals of high-performance liquid chromatography (HPLC), as applied in small-scale studies of drug stability, are presented. Chromatography is the separation of a complex mixture into its individual compounds through partitioning between a mobile phase and a stationary phase. A high-performance liquid chromatograph consists of mobile-phase reservoirs, pumps, a mixer to mix the solvents, a valve into which the sample is injected, a guard column, a column containing the stationary phase, a detector, and a recorder. Once compounds have been separated in the column, they pass into the detector, where an electronic signal corresponding to the amount of compound present is recorded as a peak in a chromatogram. The most common detection method is ultraviolet and visible light spectroscopy. Key concepts in HPLC theory are retention time, the time from injection of the sample to detection of a peak; capacity factor, a measure of retention corrected for the elution of an unretained compound; resolution, a measure of how well two peaks are separated; the selectivity of the method; efficiency, or resolving power; and the degree of symmetry of the peaks produced. Most HPLC separations are performed in the reverse-phase mode, which involves a nonpolar stationary phase and a largely polar mobile phase. Other modes are normal phase, ion exchange, and size exclusion. Before a drug stability study is carried out, an HPLC method must be developed that suits the needs of the proposed experiment. A thorough literature search is essential. Literature procedures serve as useful starting points but may require a great deal of manipulation. After the HPLC separation has been performed, it is necessary to validate the method used. It must be proved that the method is stability indicating, that the chromatographic standards were properly prepared, that the standard curve is acceptable, and that the method is both precise and accurate. Pharmacists who ensure that reliable, reproducible HPLC methods are used throughout studies of drug stability will obtain sound data that may be of great value in pharmacy practice.
The compatibility and stability of labetalol hydrochloride in combination with various critical care drugs was evaluated. Labetalol hydrochloride 1.0 mg/mL was combined in 5% dextrose injection with equal volumes of each...The compatibility and stability of labetalol hydrochloride in combination with various critical care drugs was evaluated. Labetalol hydrochloride 1.0 mg/mL was combined in 5% dextrose injection with equal volumes of each of the following drugs: dobutamine 2.5 mg/mL (as the hydrochloride salt), dopamine hydrochloride 1.6 mg/mL, morphine sulfate 0.5 mg/mL, nitroglycerin 0.2 mg/mL, and ranitidine 0.6 mg/mL (as the hydrochloride salt). The mixtures were placed in duplicate Y-site administration sets. Visual inspection, pH determination, and high-performance liquid chromatography were performed in duplicate on samples removed at zero, two, and four hours. No change in pH or appearance occurred throughout the study. All drug concentrations remained above 90% of the initial concentration in each combination. Labetalol hydrochloride 1.0 mg/mL and dobutamine 2.5 mg/mL (as the hydrochloride salt), dopamine hydrochloride 1.6 mg/mL, morphine sulfate 0.5 mg/mL, nitroglycerin 0.2 mg/mL, or ranitidine 0.6 mg/mL (as the hydrochloride salt) in 5% dextrose injection were stable and compatible for up to four hours at 20-25 degrees C during simulated Y-site injection.
A computerized system for documenting interventions, developed by the pharmacy department at a 695-bed tertiary care university teaching hospital, is described. A computerized system was developed to better gain the need...A computerized system for documenting interventions, developed by the pharmacy department at a 695-bed tertiary care university teaching hospital, is described. A computerized system was developed to better gain the needed details on pharmacists' recommendations, to capture a greater number of such recommendations, and to prepare for recent changes in standards of the Joint Commission on Accreditation of Healthcare Organizations. Only clinically important recommendations or those that involve cost savings are documented. Data can be entered and retrieved from any medical information system terminal in the hospital, and each entry becomes part of the patient's permanent record. A hard copy of all recommendations and a data file are generated daily. Analysis of the data has provided numerous opportunities for improving both patient care and the quality of pharmaceutical services. The system has been well received by pharmacists and has resulted in physician support of pharmacists' recommendations, as well as substantial cost savings. A convenient, easy-to-use computerized program for reporting interventions has helped a pharmacy department conduct departmental and institutional quality assurance activities and decrease costs.
The Cockcroft-Gault and Salazar-Corcoran equations were compared with respect to prediction of gentamicin pharmacokinetic values in obese and nonobese patients, and the results were used to formulate guidelines for calcu...The Cockcroft-Gault and Salazar-Corcoran equations were compared with respect to prediction of gentamicin pharmacokinetic values in obese and nonobese patients, and the results were used to formulate guidelines for calculating initial gentamicin dosages in obese patients. Creatinine clearance (CLcr) was estimated by applying the Cockcroft-Gault equation using total body weight (TBW), ideal body weight (IBW), and dosage weight (DW) and with Salazar-Corcoran equations using fat-free body mass (FBM) in 100 obese and 100 nonobese patients. Gentamicin pharmacokinetic values (k, CL, and t1/2) were estimated by using CLcr estimated by each method and standardized to a body surface area of 1.73 sq m. Actual pharmacokinetic values were determined by using steady-state gentamicin concentrations and a modified Sawchuk-Zaske equation; these values were compared with the predicted values. In the obese patients, pharmacokinetic values predicted from standardized CLcr by the Cockcroft-Gault equation using estimated DW were not significantly biased, compared with actual values; most predictions produced by the other methods were significantly biased. Predictions produced by the DW method were generally more precise than those resulting from the other methods. In nonobese patients, k values estimated by the Cockcroft-Gault equation using IBW were not significantly biased, while values obtained with all other methods were biased. All methods were biased when predicting CL and t1/2 in nonobese patients. Significant correlations existed between standardized estimates of CLcr (by all methods) and pharmacokinetic values in both groups. Predictions of gentamicin k, CL, and t1/2 were best overall when CLcr was estimated by the Cockcroft-Gault equation using DW, rather than by other methods.(ABSTRACT TRUNCATED AT 250 WORDS)
The physical compatibility and chemical stability of ondansetron hydrochloride 0.1 and 1 mg/mL with morphine sulfate 1 mg/mL and with hydromorphone hydrochloride 0.5 mg/mL in 0.9% sodium chloride injection were studied....The physical compatibility and chemical stability of ondansetron hydrochloride 0.1 and 1 mg/mL with morphine sulfate 1 mg/mL and with hydromorphone hydrochloride 0.5 mg/mL in 0.9% sodium chloride injection were studied. Test solutions of the drugs in 0.9% sodium chloride injection were prepared in triplicate and stored at 4, 22, and 32 degrees C. Samples were removed immediately and at various time points over 31 days and stored at -70 degrees C until analyzed. Physical compatibility was assessed visually and by measuring turbidity with a color-correcting turbidimeter and particle content with a light-obscuration particle sizer and counter. Chemical stability was determined by measuring the concentration of each drug in duplicate with stability-indicating high-performance liquid chromatography. There were no visual or subvisual changes in turbidity or particle content in any of the test solutions at any of the time points. There was little or no loss of any of the drugs. When admixed in 0.9% sodium chloride injection, ondansetron hydrochloride 0.1 and 1 mg/mL plus morphine sulfate 1 mg/mL or hydromorphone hydrochloride 0.5 mg/mL were compatible and stable for at least 7 days at 32 degrees C and for at least 31 days at 4 and 22 degrees C.