Detection of Drugs and Their Metabolites in Oral Fluid
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About this ebook
Detection of Drugs and Their Metabolites in Oral Fluid presents the analytical chemistry methods used for the detection and quantification of drugs and their metabolites in human oral fluid. The authors summarize the state of the science, including its strengths, weaknesses, unmet methodological needs, and cutting-edge trends. This volume covers the salient aspects of oral fluid drug testing, including specimen collection and handling, initial testing, point of collection testing (POCT), specimen validity testing (SVT), and confirmatory and proficiency testing. Analytes discussed include amphetamines, cannabinoids, cocaine, opiates, phencyclidine, cannabimimetics, and miscellaneous drugs.
This practical guide helps users turn knowledge into practice, moving logically from an outline of the problem, to the evaluation of the appropriateness of oral fluid as a test medium, and finally to a consideration of detection methods and their validation and employment.
- Compares different collection and testing systems to assist readers involved in clinical or forensic practice in selecting oral fluid as the matrix of choice
- Provides a sound basis for the detection of drugs and their metabolites in oral fluid and the interpretation of both positive and negative
- Places the need, or lack thereof, for specimen validity testing and confirmation testing in context with the purposes of oral fluid testing
- Describes drugs and drug classes that can be tested, along with useful information on a patient/donor’s drug status
Robert M. White
Dr. Robert M. White, Sr., retired in 2017 from his position as Senior Forensic Scientist at the Center for Forensic Sciences, RTI International, Research Triangle Park, NC, USA, and is currently the Registered Agent for RMW Consulting, Inc., Naples, FL. He has extensive experience in risk assessment, legal consulting, and federal and College of American Pathologists (CAP) inspections. Dr. White also has significant experience with conducting forensic and clinical drug testing.
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Detection of Drugs and Their Metabolites in Oral Fluid - Robert M. White
book.
Chapter 1
Introduction
Abstract
To lay the foundation for understanding how oral fluid testing works, the chapter begins with the anatomy and physiology of saliva production, saliva being the major constituent of oral fluid and, thus, the matrix for drugs and their metabolites entering the oral cavity from the blood stream. The effects of diurnal cycle and of degree and type of gland stimulation of the donor on output volume and chemical parameters are tabulated, and the complexity and variability of constituents of the oral environment, thus of oral fluid, are noted. Diseases and injuries can disrupt saliva output. Anticholinergics are notorious for producing dry mouth through action on the parasympathetic nervous system, whether the anticholinergic effect is the targeted therapeutic mechanism of action or a side effect of drugs targeted at other receptors. This reduction in the volume of the oral fluid complicates measurement of drug levels. Drugs that stimulate the parasympathetic system and increase saliva flow also are mentioned. Oral fluid pharmacokinetics for most of the commonly encountered drugs is discussed in general and by specific substance.
Keywords
Oral fluid; saliva; xerostomia; saliva production; saliva constituents; drug testing; pharmacokinetics; parasympathetic nervous system
General
Before considering oral fluid as a matrix for drug and drug metabolite testing, it is worthwhile describing the sources and formation of human oral fluid in order to understand its strong points and limitations.
Saliva, the major component of oral fluid, is produced primarily by three bilateral pairs of salivary glands: parotid, submandibular, and sublingual, as summarized in Table 1.1.¹
Table 1.1
Fig. 1.1 shows the approximate location of each pair of glands.²
Figure 1.1 Approximate locations of major human salivary glands.
Minor accessory salivary glands, which are about 450–750 in number, are located on the tongue, the buccal mucosa of the lips, and the palate. They do not have a common duct, and they produce a viscous secrete.¹ Von Ebner’s glands (not shown in Fig. 1.1), which are oral exocrine glands that in part secrete lipase, are serous glands that reside at the base of the crypts that surround the circumvallate and foliate papillae on the tongue, just anterior to the posterior third of the tongue.³
A healthy individual produces about 500–1500 mL of saliva per day, which is about 0–6 mL per minute, depending highly on whether the individual is awake or asleep and whether the salivary glands are stimulated or not, as illustrated in Table 1.2.¹
Table 1.2
aThis type of stimulation may be accomplished by chewing on an inert substance such as paraffin.
bAlso called gustatory stimulation.
A salivary gland consists of acini and a duct that leads either directly to the oral cavity or to a common duct that leads to the oral cavity. Fig. 1.2 shows that circulating blood exchanges components at the acini and the ductus.² In both areas, a capillary bed exists to facilitate the exchange.
Figure 1.2 Mechanisms of transport of proteins and ions from plasma into the salivary ducts. a, ultrafiltration; b, active transport or passive diffusion across the cell membrane; c, simple filtration through cell membrane pores; d, transepithelial movement of water along NaCl gradient via channel proteins; e, creation of hypotonic salivary solution via ductal Na+ reabsorption; f, acinar cell membrane; g, cell membrane pore; h, intercellular space; i, acinar cell.
In Fig. 1.2, it is most notable that several pathways, not just simple filtration, exist for the transfer of small molecules such as drugs and drug metabolites from capillary plasma into saliva that is being formed in the salivary gland.
Saliva becomes oral fluid when formed saliva enters the oral cavity and mixes with crevicular fluid, which contains small amounts of normal human plasma constituents such as immunoglobulin G (IgG), oral cavity microbes, nasopharyngeal secretions, and any food particles that may be present.
The actions of the acini produce an ultrafiltrate of blood with a composition that is vastly different from plasma, which is the noncellular component of whole blood (as illustrated in Table 1.3) from which the oral fluid was derived.²,³
Table 1.3