Maurer H H, Fritz C F
Institut für Pharmakologie und Toxikologie, Universität des Saarlandes, Federal Republic of Germany.
Int J Legal Med. 1990 Dec;104(1):43-6. doi: 10.1007/BF01816483.
Pholcodine (3-O-(2'-morpholinoethyl)-morphine) is used in many countries as an antitussive without analgesic or addictive properties. It is of forensic relevance that pholcodine interferes with opiate immunoassays. In this paper a gas chromatographic-mass spectrometric (GC-MS) procedure for the precise and sensitive detection of pholcodine and its metabolites in urine and hair, after acid hydrolysis, extraction and acetylation, is presented. Furthermore, detection of pholcodine using radio immunoassay (RIA), fluorescence polarisation immunoassay (FPIA) and enzyme immunoassay (EIA) for opiates is described. Using GC-MS, unmodified pholcodine could be detected in urine samples 4-7 weeks after ingestion of a single therapeutic dose of 50mg of pholcodine, the desmorpholinohydroxy metabolite for 1-2 weeks and the other metabolites (nor-, nordesmorpholinohydroxy-, hydroxy-, oxo- and noroxo-pholcodine) only during the first few hours. Morphine could also be detected in urine samples for the first few days. It was however mainly formed artificially during acid hydrolysis and only in trace amounts by metabolism. All the immunoassays tested gave positive results in urine samples during the first week taking the cut-off values recommended by the manufacturer into consideration. If values between the cut-off and the detection limit were taken into consideration, RIA and FPIA gave positive results for 2-4 weeks and EIA up to 2 weeks. Pholcodine could also be detected by RIA and GC-MS in samples of head hair clipped 10 weeks after ingestion of 50mg and in daily shaved samples of beard hair over a period of three weeks after ingestion of three doses of 60mg. It can be concluded that the widely used immunoassays for opiates show positive results in urine and hair samples for a long time after ingestion of the non-opioid pholcodine and that these results can be confirmed by the GC-MS procedure described in this paper.
福尔可定（3 - O -（2'-吗啉代乙基）吗啡）在许多国家用作镇咳药，无镇痛或成瘾性。福尔可定干扰阿片类免疫测定具有法医学相关性。本文介绍了一种气相色谱 - 质谱（GC - MS）方法，用于在酸水解、萃取和乙酰化后，精确灵敏地检测尿液和毛发中的福尔可定及其代谢物。此外，还描述了使用放射免疫测定（RIA）、荧光偏振免疫测定（FPIA）和阿片类酶免疫测定（EIA）检测福尔可定的方法。使用GC - MS，在单次服用50mg福尔可定治疗剂量后4 - 7周的尿液样本中可检测到未修饰的福尔可定，去吗啉代羟基代谢物可检测1 - 2周，其他代谢物（去甲、去甲去吗啉代羟基、羟基、氧代和去甲氧代福尔可定）仅在最初几小时内可检测到。在最初几天的尿液样本中也可检测到吗啡。然而，它主要是在酸水解过程中人工形成的，通过代谢形成的量仅为痕量。考虑到制造商推荐的临界值，所有测试的免疫测定在服用福尔可定的第一周内对尿液样本均给出阳性结果。如果考虑临界值和检测限之间的值，RIA和FPIA在2 - 4周内给出阳性结果，EIA在2周内给出阳性结果。在服用50mg福尔可定10周后剪下的头发样本以及在服用三剂60mg福尔可定后三周内每日剃须得到的胡须样本中，也可通过RIA和GC - MS检测到福尔可定。可以得出结论，广泛使用的阿片类免疫测定在摄入非阿片类福尔可定后的很长一段时间内，在尿液和毛发样本中均显示阳性结果，并且本文所述的GC - MS方法可以证实这些结果。
