Stability of fentanyl citrate in glass and plastic containers and in a patient-controlled delivery system.

This study determined the stability of fentanyl citrate stored in glass or polyvinyl chloride containers and the concentrations of fentanyl citrate delivered by the Janssen on-demand analgesic computer (ODAC) system. Solutions containing 500 micrograms of fentanyl citrate (10 mL) were added to 100-mL three glass containers each of 5% dextrose injection or 0.9% sodium chloride injection and to three 100-mL polyvinyl chloride containers of 5% dextrose injection or 0.9% sodium chloride injection. All containers were stored under usual light conditions and at room temperature. Samples were taken immediately and at 0.25, 0.5, 1, 6, 12, 24, 36, and 48 hours. To determine the concentration of fentanyl delivered via the ODAC system, fentanyl citrate injection 2500 micrograms (50 mL) was added to a 500-mL polyvinyl chloride bag containing 5% dextrose injection. The solution was connected to the ODAC system, and samples of bolus demand doses were collected at various times during a 30-hour period. All the samples were assayed by a stability-indicating gas-liquid chromatographic method. For both glass and plastic containers, the mean +/- S.D. recovery of fentanyl after 48 hours was 98.6 +/- 2.3% when the drug was diluted in 5% dextrose injection and 97 +/- 1.5% when the drug was diluted in 0.9% sodium chloride injection. There was no significant difference between the amount of fentanyl recovered from glass containers and the amount recovered from polyvinyl chloride containers. Nor was there any significant difference between the amount of fentanyl recovered from solutions containing 5% dextrose injection and the amount recovered from solutions containing 0.9% sodium chloride injection.(ABSTRACT TRUNCATED AT 250 WORDS)

Fentanyl blood concentration-analgesic response relationship in the treatment of postoperative pain.

The inter- and intrasubject variability in blood concentration-analgesic response relationship for fentanyl were investigated using the technique of patient-controlled analgesia (PCA) in 30 consenting patients scheduled for surgical procedures involving an abdominal incision (15 upper and 15 lower abdominal incisions). All patients had a thiopental, nitrous oxide/oxygen, pancuronium anesthetic with 200 microgram fentanyl intraoperatively. Postoperative pain relief was provided with fentanyl from a Janssen On-Demand Analgesic Computer (ODAC) set to provide a basal infusion rate of 20 microgram/hr, a bolus "demand" dose of 20 microgram, and a lockout period of 5 minutes. Frequent blood samples were collected immediately before patients demanded doses, and these were taken as an estimate of the minimum effective concentration (MEC). A mean of 22 samples (range 12 to 45) were collected per patient over a mean study duration of 50 hours (range 24 to 72). The patients required larger hourly fentanyl doses in the first 6-hour period (83.9 +/- 30.1 microgram/hr) than in any other 6-hour period (mean values varied from 37.3 to 63 microgram/hr). The mean (+/- SD) hourly fentanyl dose rate and total cumulative dose were 55.8 +/- 22 microgram/hr (range 28.8 to 136 microgram/hr) and 2739 +/- 1191 microgram (range 900 to 6260 microgram), respectively. The mean (+/- SD) MEC was 0.63 +/- 0.25 ng/ml (five-fold range from 0.23 to 1.18) and the mean intrapatient coefficient of variation in MEC was 30.2% (range 16 to 46%). The MEC values remained relatively constant in all patients over the 48-hour study period.(ABSTRACT TRUNCATED AT 250 WORDS)

Sensitive gas liquid chromatography method for the determination of fentanyl concentrations in blood.

A method for the determination of fentanyl blood concentrations using gas liquid chromatography coupled to a nitrogen phosphorus detector (NPD) is presented. A highly inert fused-silica, megabore column coated with a methyl silicone stationary phase was used for the analysis. The mean coefficient of variation for the range of fentanyl concentrations tested (0.25-10 ng/ml) was 4.65%, ranging from 0.85% at 10 ng/ml to 10.8% at 0.25 ng/ml. The assay was used to quantify blood fentanyl concentrations collected from a 56-year-old woman who was administered fentanyl postoperatively via a patient-controlled on-demand analgesic computer (ODAC). The mean hourly fentanyl dose rate over the 44 hr study period was 41.8 micrograms/hr (range 20-120). The sixfold variation in hourly dose rate was not mirrored by similar fluctuations in the fentanyl blood concentration (mean 0.45 ng/ml, range 0.3-0.7 ng/ml). The patient thus titrated herself to a perceived minimum effective concentration (MEC) of fentanyl.