J Pharm Biomed Anal. 2000 Apr; 22(3): 481-6.

LC and LC-MS-MS analyses of undeclared codeine in antiasthmatic Chinese proprietary medicine.

Liu SY, Woo SO, Holmes MJ, Koh HL.

Department of Pharmacy, National University of Singapore, Singapore.

This paper describes an accurate and sensitive reversed phase high-performance liquid chromatographic (RP-HPLC) method for the detection and quantification of undeclared codeine in a Chinese Proprietary Medicine (CPM) for asthma. A rapid and specific liquid chromatography-mass spectrometry-mass spectrometry (LC-MS-MS) method was applied to confirm the presence of codeine by selected reaction monitoring (SRM). Codeine was extracted from the capsules by dissolving in sodium dihydrogen phosphate buffer (10 mM, pH = 2.2) and ethanol, then made alkaline (pH = 9) and extracted using chloroform. The amount of codeine in AsthmaWan was found to be 61.8 microg/capsule (R.S.D. = 7.9%, n = 9). Excellent resolution was obtained despite the complexity of the product which claimed to contain at least nine herbal ingredients, none of which will give rise to codeine. As a further confirmation method, LC-MS-MS is accurate and specific. The LC method has been validated for linearity, limit of detection, limit of quantification, accuracy and specificity. Greater awareness of and control over undeclared drugs in complementary medicine are necessary to ensure patients' safety.