To determine whether saliva concentrations of morphine sulfate correlate with plasma levels of morphine in pediatric patients receiving morphine analgesia for severe pain, to determine the effect of pH on the analytical measurement of morphine in stimulated saliva, and to evaluate the usefulness of an enzyme immunoassay (EIA) to measure morphine concentrations in saliva.

Fifteen pediatric patients were enrolled; for the control group, 18 adult volunteers were recruited. Patients received continuous morphine drips (range: 10 - 40 μg/kg/hr). Control subjects were randomized into receiving either acetaminophen (Tylenol #1) with 8 mg codeine (N = 13) or acetaminophen(Tylenol #3) with 30 mg codeine (N = 5). All participants were nil per os at least 2 hours prior to sample collection. Blood samples were obtained by venipuncture followed by a saliva sample collected with a mucous extractor in infants or by expectorating directly into a labeled tube when possible. In all subjects, citric acid, 5 - 10 mg, was used to stimulate salivation. The pH of each sample was measured. All samples were centrifuged and stored at -20°C until analysis. All samples were analyzed with a modified Count-A-Count® serum morphine radioimmunoassay (RIA) kit. Morphine concentrations in plasma and saliva were compared by a linear regression analysis (95% confidence limits). All results reported are mean ± standard deviation (SD).

There was no correlation between saliva and plasma morphine concentrations in the patient group (r = 0.04). There was also no correlation in the adult control group (r = 0.43). The mean saliva to plasma ratio was 2.28 in patients and 1.31 for the controls. There was a preference in the pediatric patient group for saliva sampling. There was no observed difference in the mean counts per minute (CPM) for saliva samples in the pH range 3.96 to 8.06 (11537± 255 CPM). The sensitivity of the EIA (300 ng/mL) precludes its use to measure typical clinical levels of morphine in saliva and blood.

Saliva does not predict the plasma concentration of morphine in children or adults. However, the concentration of morphine in saliva can be used as a qualitative indicator of the presence or absence of morphine in the subject. The pH of saliva samples does not need to be pH-adjusted prior to RIA and the EIA cannot be used to measure typical clinical levels of morphine in either sample media.