Drugs may arise from unexpected sources including food and over-the-counter (OTC) medicines. Quinine may originate from ingestion of tonic water or malaria prophylaxis, for example, caffeine from caffeinated beverages (tea, coffee, cola) and some proprietary stimulants, chloroquine, and related compounds from malaria prophylaxis, and pholcodine and other opiate analogues from cough and cold cures. Morphine is a constituent of some antidiarrhoeal preparations and is present in poppy seeds. A caffeine metabolite, paraxanthine, may be a problem in some LC theophylline assays.
Lidocaine-containing gel is commonly used as a lubricant during procedures such as bladder catheterization or bronchoscopy, and measurable plasma concentrations of lidocaine and some metabolites may be attained. Lidocaine and propofol are commonly used in association with emergency procedures, but these compounds may be misused together. Ketamine and morphine may also be given as part of emergency procedures. The alkaloids emetine and cephaeline, and their metabolites, have been detected in stomach contents, plasma, and in urine after syrup of ipecacuanha (ipecac) was given to induce vomiting, especially in children, although this form of treatment is no longer recommended practice.
Sedatives such as pethidine (meperidine) may be given prior to computerized tomographic (CT) scans, lumbar puncture, or other investigations. Neuromuscular blocking agents such as atracurium, which is metabolized to laudanosine, and vecuronium, may be encountered in samples from patients undergoing mechanical ventilation. 1,3-Propanediol (propylene glycol) is used as a vehicle in some i.v. infusions. Benzoic acid, which is metabolized to hippuric acid, is used as a preservative in some drugs and foods.
The antibiotic metronidazole is often encountered in samples from hospitalized patients. Medical imaging media may interfere in a range of assays (Lippi et al., 2014). Alcohols may originate from skin cleansing swabs. Such compounds and also drugs given in emergencies, amiodarone, anticonvulsants such as diazepam, and propofol, for example, may not be recorded on record sheets. Some compounds or their metabolites may have very long plasma half-lives. Chlorpromazine metabolites, for example, have been reported in urine many months after stopping therapy. Primary amines and even morphine, for example, can be acetylated in gastric contents if aspirin has been co-ingested (Naso-Kaspar et al., 2013).
Contamination with trace elements is a particularly difficult area (Chapter 21). Contamination with volatiles, such as solvents used in the laboratory, must be guarded against if one of the solvents in question is to be tested for in a biological or related sample. Glassware and other items must be kept clean and tested regularly for contamination via IQC procedures.
2.6 Summary
Although not in the immediate control of the laboratory, every effort must be made to ensure appropriate priority is given to sample collection and handling because if this is not done properly all subsequent effort is wasted. Care in sample collection is especially important in post-mortem and overt medico-legal work, but even in clinical work effort in providing advance information to clinicians and pathologists on sample requirements (site of collection, volume, addition of sodium fluoride, etc.) and feedback on the problems that will arise when mistakes are made can only prove beneficial.
References
1 Ameline A, Raul JS, Kintz P. Testing for midazolam and oxycodone in blood after formalin-embalmment: About a complex medico-legal case. Drug Test Anal 2019; 11: 1460–4.
2 Arora B, Velpandian T, Saxena R, Lalwani S, Dogra TD, Ghose S. Development and validation of an ESI-LC-MS/MS method for simultaneous identification and quantification of 24 analytes of forensic relevance in vitreous humour, whole blood and plasma. Drug Test Anal 2016; 8: 86–97.
3 Arslan Z, Athiraman NK, Clark SJ. Lithium toxicity in a neonate owing to false elevation of blood lithium levels caused by contamination in a lithium heparin container: Case report and review of the literature. Paediatr Int Child Hlth 2016; 36: 240–2.
4 Baselt RC. Disposition of Toxic Drugs and Chemicals in Man. Edition 12. Seal Beach: Biomedical Publications, 2020.
5 Belsey SL, Flanagan RJ. Postmortem biochemistry: Current applications. J Forensic Leg Med 2016; 41: 49–57.
6 Berk SI, Litwin AH, Du Y, Cruikshank G, Gourevitch MN, Arnsten JH. False reduction in serum methadone concentrations by BD Vacutainer serum separator tubes (SSTTM). Clin Chem 2006; 52: 1972–4.
7 Bévalot F, Cartiser N, Bottinelli C, Guitton J, Fanton L. State of the art in bile analysis in forensic toxicology. Forensic Sci Int 2016; 259: 133–54.
8 Bowen RA, Remaley AT. Interferences from blood collection tube components on clinical chemistry assays. Biochem Med (Zagreb) 2014; 24: 31–44.
9 Cartiser N, Bévalot F, Fanton L, Gaillard Y, Guitton J. State-of-the-art of bone marrow analysis in forensic toxicology: A review. Int J Legal Med 2011; 125: 181–98.
10 Castellanos M, Xifra G, Fernández-Real JM, Sánchez JM. Breath gas concentrations mirror exposure to sevoflurane and isopropyl alcohol in hospital environments in non-occupational conditions. J Breath Res 2016; 10: 016001.
11 Day RO, McLachlan AJ, Graham GG, Williams KM. Pharmacokinetics of nonsteroidal anti-inflammatory drugs in synovial fluid. Clin Pharmacokinet 1999; 36: 191–210.
12 Dinis-Oliveira RJ, Carvalho F, Duarte JA, Remião F, Marques A, et al. Collection of biological samples in forensic toxicology. Toxicol Mech Method 2010; 20: 363–414.
13 Dinis-Oliveira RJ, Vieira DN, Magalhães T. Guidelines for collection of biological samples for clinical and forensic toxicological analysis. Forensic Sci Res 2017; 1: 42–51.
14 Dong H, Zhang FJ, Wang FY, Wang YY, Guo J, et al. Simultaneous on-line monitoring of propofol and sevoflurane in balanced anesthesia by direct resistive heating gas chromatography. J Chromatogr A 2017; 1506: 93–100.
15 Fabresse N, Fall F, Etting I, Devillier P, Alvarez JC, Grassin-Delyle S. LC-MS/MS determination of tranexamic acid in human plasma after phospholipid clean-up. J Pharm Biomed Anal 2017; 141: 149–56.
16 Ferner RE, Aronson JK. The toxicological significance of post-mortem drug concentrations in bile. Clin Toxicol (Phila) 2018; 56: 7–14.
17 Foley KF. A positive urine alcohol with negative urine ethyl-glucuronide. Lab Med 2018; 49: 276–9.
18 Freeman JD, Rosman LM, Ratcliff JD, Strickland PT, Graham DR, Silbergeld EK. State of the science in dried blood spots. Clin Chem 2018; 64: 656–79.
19 Handley SA, Silk SW, Handley DS, Subramaniam K, Flanagan RJ. Clozapine and norclozapine concentrations in paired human plasma and serum samples. Ther Drug Monit 2018; 40: 148–50.
20 Hanouneh M, Chen TK. Calcium oxalate crystals in ethylene glycol toxicity. N Engl J Med 2017; 377: 1467.
21 Heussner K, Rauh M, Cordasic N, Menendez-Castro C, Huebner H, et al. Adhesive blood microsampling systems for steroid measurement via LC-MS/MS in the rat. Steroids 2017; 120: 1–6.
22 Introna F, Campobasso CP, Goff ML. Entomotoxicology. Forensic Sci Int 2001; 120: 42–7.
23 John H, Willoh S, Hörmann P, Siegert M, Vondran A, Thiermann H. Procedures for analysis of dried plasma using microsampling devices to detect sulfur mustard-albumin adducts for verification of poisoning. Anal Chem 2016; 88: 8787–94.
24 Kip AE, Kiers KC, Rosing H, Schellens JHM, Beijnen JH, Dorlo TPC. Volumetric absorptive microsampling (VAMS) as an alternative to conventional dried blood spots in the quantification of miltefosine in dried blood samples. J Pharm Biomed Anal 2017; 135: 160–6.
25 Kok MGM, Fillet M. Volumetric absorptive microsampling: Current advances and applications. J Pharm Biomed Anal 2018; 147: 288–96.
26 Krumbiegel F,