Interpretation of GC-MS opiate results in the presence of pholcodine

Although the cross reactivity of pholcodine with opiate immunoassays has been well documented there is little published information the potential for pholcodine interference with chromatographic analyses. Wilson and Smith [Ann. Clin. Biochem. 36 (1999) 592] recently described the 'misidentification' of morphine in quality control specimens that had been spiked with pholcodine. This report describes a sensitive, rapid gas chromatography-mass spectrometry (GC-MS) method for the detection and quantitation of pholcodine and morphine, together with 6-monoacetylmorphine (6-MAM), codeine and dihydrocodeine in urine. This method was used to analyse urine specimens collected from volunteers given single and multiple doses of pholcodine to establish the significance this drug on the analytical results obtained when performing drug screening according to the proposed UK and EU legally defensible workplace drug testing guidelines. The maximum urinary free morphine concentration achieved following a single 10mg oral dose of pholcodine was 1.39 mg/l at 2-4h post dose. Following multiple 10mg oral doses of pholcodine the maximum urinary free morphine concentration was determined as 0.4 mg/l at 170 h after the final dose was administered. This apparent anomaly in the morphine concentrations obtained following single and multiple pholcodine doses can be explained in part by differences in the concentration of the specimens, and may be overcome by applying a correction factor for specimen dilution using their creatinine concentration. The data from this study suggests that even following one single 10mg dose of pholcodine, free morphine concentrations greater than both the proposed UK workplace drug testing guidelines threshold of 0.3mg/l total morphine and the proposed European Union threshold of 0.2mg/l total morphine can be achieved. This highlights the need for caution when interpreting confirmatory opiate data, especially in medicolegal and clinical cases, and in cases where the use of pholcodine is suspected.