Problems of Urine Screening

Morgan, John, "Problems of Urine Screening." Journal of Psychoactive Drugs. 1984; 16(4): pp. 305-317.

Introduction

In 1984, a careful study under field conditions by Kleinmutz and Szucko called into question the ability of
the polygraph and its interpreters to detect lies: "...our findings show high false-positive and false-negative
rates among polygraph interpreters.... we conclude that the validity and reliability of polygraphic
interrogation has yet to be established." It is doubtful that this critical study will eliminate the use of the lie
detector. Its presence, however technically flawed, has great symbolic utility. Its application satisfies the
powerful desire to know intimate and hidden details of the moral behavior of humans.

The desire to know about secret drug use may be nearly as compelling as the wish to discern lying. A
commitment to drug detection technology is developing in a similarly uncritical fashion.

There are widely accepted justifications for drug testing. Individuals in treatment or probationary programs
may be required to submit to urine monitoring as evidence of their commitment to the program, which they
even may have joined to avoid incarceration. Individuals in the workplace who have been involved in
accidents are sometimes subjected to mandatory testing. The desire to know if a motorman caused an
accident because of careless drug use is understandable and corresponds to assessing ethanol
concentration in those involved in nonwork-related vehicular accidents.

None of these preceding categories anticipates the mass screening of overtly functional people who,
because of employment, military or prisoner status, are subjected to mandates to offer up their urine for
drug testing. Not only is this a new phenomenon, but it places the drug-positive individual in the grim
situation of proving his/her innocence - not of intoxicated dysfunction or malfeasance, but of immoral and
undesirable behavior. The usual justifications offered for mass screening do not withstand examination.

These proceedings contain a number of references to the cost of drug abuse to American industry (e.g.,
Cohen 1983). Most of these estimates are extrapolations and projections that have no convincing data
base. The cost estimates are derived from a set of seldom questioned but surely questionable
assumptions. These include the belief that dysfunctional work (or life) and a history of use or presence of a
drug are causally associated, and the assumption that all who use drugs are sure and soon to malfunction
in a fashion similar to the drug abusers seen in treatment programs.

These assumptions are pervasive and are often stated to justify compulsive monitoring on the grounds of
imminent danger to the user or other workers, lapses in security or the need to detect drug use in order to
intervene with treatment. Such justifications are part of the operational process of "medicalization" of
ethical and political conflicts. Medicalization increases the options of controlling conflicts and problems
without protest because there is little argument possible against medical language, predefined as humane
(Roman 1980). In truth, these excuses are weak for two important reasons. There is almost no proven
correlation between any positive urinary test for drugs and observed or assessed human behavior. The
tests that assess the drugs of most current interest (marijuana and cocaine) measure metabolites of the
drug that persist for hours or days after use. Therefore, any positive test cannot be used in an assessment
of work-related dysfunction because it might well reflect recreational or even work-related use well in the
past. Moreover, the descriptions of supposed malfunction all ignore an experimental and anecdotal history
of drug use that improves work performance. Both ancient Peruvian miners (Helms 1975) and modern
Jamaican workers (Rubin & Comitas 1975) have been characterized as working better under drug
influence. A variety of studies have indicated that stimulant drug use may increase productivity in a variety
of settings (Weiss & Laties 1962). Modern cultural belief and conventional wisdom demand that such
evidence be explained away or ignored.

The real justification for the screening of urine in industry or elsewhere is the identification of deviant
behavior. That identification may be followed by segregation, punishment, firing, surveillance, treatment or
any of a variety of interventions, humane or inhumane. The conventional excuses for the humane
treatment should not obscure the fact that urine screening is a probe to identify deviance, not dysfunction -
a technique to investigate humans, not accidents.

Drug Testing and Analogy

The appropriate first step in a needed demystification of analytical toxicology is to point out that it, like all
quantitative analysis, is indirect and constitutes analogy. The polygraph is based on the apparently
incorrect analogy that variations in some physiological measurements (i.e., pulse, blood pressure, galvanic
skin conductance) may be viewed as if they were a reflection of lying. Urine cannot be peered into to see
the tiny components of a dissolved drug. Techniques and manipulations are used that reflect and amplify
some character of the drug molecule: its binding to other chemicals, its migration with a solvent along a
piece of paper or its character when ignited. Each analogue measurement and each drug may require
many steps and each step may provoke error. Drug measurement is not easy. Precision drug
measurement is even harder.

Drug testing is compared to other analogies to demystify it, not to demean it. The analytical methods and
their developments reflect impressively skillful science and technology. Tests to identify drugs are all the
more impressive because at times the analogy is so exact that it saves lives. However, the process should
be described as it is and what it is: an indirect reflection of a solute in a mixed solution.

Methods With a Focus on Enzyme Multiplied Immunoassay

There are many methods in analytical drug-screening technology. All of these methods will not be
reviewed here and the interested reader is referred elsewhere (Caplan 1981; Thoma, Bondo & Sunshine
1977). Furthermore, many methods are in current use for drug screening, including enzyme multiplied
immunoassay (EMIT®), radioimmunoassay (RIA) and thin-layer chromatography (TLC). EMIT® is widely
used in screening, but is almost certainly less often used than RIA. One important reason for this is the
decision of the United States Department of Defense to rely on the RIA as its primary method of urine
screening.

The principal reason for choosing EMIT® as a focus for consideration is its marketing as a test to be done
on site by personnel not primarily trained as laboratory workers (Syva Corporation 1982), "because they
[EMIT® tests] do not require specially licensed personnel, subjective interpretation of results or special
handling techniques and safety precautions, they can be run by any trained staff member." This marketing
of the product for noncentralized testing makes EMIT® the test that most needs demystifying. The Syva
Corporation (1983) has even established a marketing entity called Performance Diagnostics that was
"...formed to help companies evaluate the presence or extent of the drug and alcohol problem in the
workplace." This service by Performance Diagnostics often includes the recommendation of EMIT® testing
to the client company staff for on-site testing. The RIA, because of its use of radioactive isotopes, must
generally be used in a licensed laboratory facility, although a large or moderately sized company could
easily obtain a license for an on-site laboratory.

In 1972, Rubenstein and his co-workers published the first details of a "homogenous enzyme
immunoassay." Others labeled it an enzyme multiplied immunological technique, hence the acronym
EMIT®, which is a trademark of the Syva Corporation.

The technique relies on modifying an enzyme's ability to act on its substrate. The presence of a drug
modifies the action of a lysozyme (or other enzyme). This lysozyme ordinarily will dissolve a constituent of
bacterial cell wall and cause a cloudy suspension of bacteria to dissolve and become clear. The changes
in turbidity are measured by the changes in the passage or absorbance of a beam of light. Critical to the
success of EMIT® is the use of immunological chemistry. An animal is injected with a drug or drug
metabolite, usually in combination with other chemicals. This injection provokes the animal to produce
specific immune chemicals that will bind to the drug. These antibodies to drug antigens are then harvested
by extracting and purifying certain proteins (gamma globulins) from the animal's blood.

The lysozyme or other enzyme is bound to the drug or metabolite of interest (e.g., morphine,
amphetamine, methadone). This drug-enzyme complex is inactivated as a functional enzyme when the
drug antibody is placed in the same solution. In other words, the antibody to the specific drug will inactivate
an enzyme bound to the drug. If, however, an added urine sample contains the drug in question, the
antibody will bind less of the drug-enzyme complex because said antibody now binds to its destiny, the
free drug. Any unbound drug-enzyme is active and lyses the bacterial suspension from micrococcus
luteus, clearing the solution (see Figure 1). This clearing is measured as a change in absorbance of light
using a spectrophotometer. This wordy explanation is represented symbolically in Figure 2.

FIGURE 2

Du + Ab + (D - Enz) ( Ab - Du + D - Enz *

Substrate + D - Enz * ( Product

D=drug
Du=urinary drug
Ab=antibody
Enz=enzyme
*=activation
-=binding

The term "substrate," in the usual application, describes the bacterial cell wall constituent and "product"
represents the material substrate now solubilized by the lytic process. The term "homogenous" is used
because this mixture does not require a separation stage common to most other immunoassays. (The RIA
depends on a very similar process in which an antibody, similarly produced, binds both the drug from
tested urine and added radioactively labeled drug so that an assessment of bound versus unbound
radioactivity reflects the drug's presence.) The term "multiplied" refers to the concept that one molecule of
drug frees one molecule of enzyme, which in turn can catalyze the lysis of many molecules of cell wall
substance.

EMIT® assays are now available in a variety of kits for screening urine for amphetamine, barbiturates,
benzodiazepines, cocaine metabolite, methadone, phencyclidine, morphine, propoxyphene, ethanol, and
urinary cannabinoids that are metabolites of marijuana. The EMIT® method employs several different
enzyme systems available in different assay products. Lysozyme (derived from egg white) is used in the
EMIT-dau® system, which can reflect opiates, barbiturates, amphetamine, benzodiazepines, cocaine
metabolite, methadone and propoxyphene. Malate dehydrogenase is used both in the EMIT-dau® and the
EMIT-st® cannabinoid assays. Glucose-6-phosphate dehydrogenase (G6PDH) is used in EMIT-dau®
tests for methadone and phencyclidine as well as other EMIT-st® versions of compounds listed in the
above EMIT-dau® examples. The EMIT-st® version for ethanol requires alcohol dehyrogenase. These
alternate enzymes are all activated as described above, but have different substrates that lead to
absorbance changes measured spectrophotometriclly. The EMIT-st® tests are designed to reflect only the
presence or absence of the drug and are qualitative. The EMIT-dau® systems incorporate a series of
standard solutions ("calibrators") that in comparison to the sample can yield a semi-quantitative analysis.

In summary, the EMIT® tests utilize complex immunochemistry and the production of drug antibodies in
interaction with enzymic detectors to reflect the presence of various drugs subject to misuse. Of course,
the method can be used to assess other chemicals, both therapeutic and toxic. With this background,
some specific issues can be discussed, particularly in light of current marketing thrusts toward primary on-
site drug screening.

Sensitivity and False Negatives

The EMIT® method is very sensitive and false negatives rarely occur. Table I lists levels of detection in the
urine for some of the most important drugs of interest. Of course, it is possible that a drug assay reported
as negative may contain very small amounts of a drug or be very diluted by large urine volumes, but this
test meets an important requirement of a screening test in that it reliably reflects small amounts of the
drug. However, some factors may alter this sensitivity. EMIT® performs optimally when urine pH ranges
between 5.5 to 8.0. Samples that are old may have undergone significant pH change and are likely to
present false negatives because such changes may alter enzyme function, among other factors. The
addition of NaCl in concentrations of 20 mg/ml probably inactivates enzyme activity because of ionic
effects and, thus, all EMIT® tests become negative (Kim & Cerceo 1976). Other ionizing salts placed in
urine may also yield this effect and a measure of specific conductivity shows a negative correlation with
EMIT® function (Anderson & Erikson 1977). Whether this factor is being exploited by drug users is
unknown, but at some point very close observation of voiding could become a mass event as well.

Specificity and False Positives

Conceptually, a false-positive result is easily understood. Can a sensitive test be positive when the drug
sought is not there? The answer is clearly yes. In a research situation or a nonpunitive screening, even a
high false-positive rate is of minimal importance. However, in a screening program directed at
probationers, individuals undergoing preemployment or prepromotion examinations or job fitness
evaluations, the reporting of a drug-positive urine takes on great social significance. The occurrence of a
false positive is much more important then a false negative. As with most politically important terms, the
definition of "false positive" is subject to tedious argument. Proponents of and apologists for screening
prefer the term "unconfirmed positive." The rhetorical implication of such a stance is clear. If one has
merely not confirmed the positive then it still may have been a positive. This is not far from sophistry. In
fact, the choice of the phrase signals the necessity to confirm all positives, simply because the EMIT® test
(and other immunoassays) are less specific than one would wish. The issue of confirmation will be
discussed further. Generally, a false positive is by definition equivalent to an unconfirmed positive when a
reasonable attempt has been made to confirm by using an analytical test that exploits a different screening
method and is at least as sensitive as EMIT®. The failure to confirm EMIT® may occur for several
reasons. First, positive reactions may occur due to a carry-over following a preceding sample that was
strongly positive (Syva Corporation 1982). To this might be added other operator errors, such as
contamination of other equipment or failure to cleanse glassware. Operator error, present to some degree
in all technologies, requires emphasis in a proposed on-site system using nonspecialist personnel.
Second, positive reactions may occur due to the reactive presence of other chemicals that bind to a
particular antibody and, third, positive reactions may, occur due to endogenous human urinary enzymes
that mimic the effects of the detector enzymes.
In addition, false-positive reactions may occur for reasons still unknown. Perhaps the technology that binds
a large enzyme to a small drug molecule is not error free.

Cross-Reactivity

According to Bost, Sutheimer and Sunshine (1976), "The greatest defect of immunoassays is their lack of
specificity. Very few anti-sera exist that are specific for a single compound, although some have been
prepared with very high specificity where cost was no object. Hence one should confirm all positive results
by some other procedure if specificity is important. Clearly, it is essential to know what specific substance
is present in certain forensic medicine problems because (e.g.) a job may be in jeopardy or a potential
parole violator incarcerated."

Antibodies to drug antigens are variously nonspecific and may bind to other chemicals. For example, the
EMIT® antibody, which is produced by the injection of a nitrogen substituted amphetamine-protein
conjugate, cross acts with a large number of phenylisopropylamines, some of which have importance in
clinical medicine. In fact, methamphetamine and ethylamphetamine react more strongly with the
amphetamine antibody than does amphetamine (Budd 1981a).

The commonly used over-the-counter (OTC) phenylisopropylamines, ephedrine and phenylpropanolamine

(PPA), react with the antibody in clinically obtained concentrations (Budd 1981a). Some cross-reactivity
may be advantageous to the goals of screening. The appearance of either amphetamine or
methamphetamine will cause reactivity and both are misused drugs. However, the appearance of
counterfeit amphetamine has become common (Morgan & Kagan 1978). Previously popular amphetamine
formats are manufactured using a variety of less potent stimulant drugs, such as PPA, ephedrine and
caffeine. Many amphetamine positives via EMIT® are likely to be nonamphetamine products resultant from
the counterfeits or from legitimate cold-cough or antiasthmatic products.

Aware of this problem, Syva Corporation sells an amphetamine confirmation kit that depends on
differentiation (after chemical reaction) of products with the ß-hvdroxyl group, such as PPA and ephedrine,
from those without, such as amphetamine and methamphetamine (see Figure 3).

One is likely to provoke an argument with EMIT® enthusiasts if one calls a positive amphetamine screen
that was caused by PPA in Sinu-Tab® a false positive. However, this author wishes to do so. If one
encounters a positive test for amphetamine and then in turn spends money on an amphetamine
confirmation test that is negative and confirmatory gas-liquid chromatography that reveals that the product
is PPA or ephedrine, one might as well face up to the difficulty and call it a false positive.

The cross-reactivity by which the opiate test is positive for heroin is lauded. However, this test will also be
positive for legitimate codeine and hydromorphone or a popular ingredient of cough syrups in Europe,
pholcodine (Svenneby, Wedege & Karlsen 1983).

The issue of cross-reactivity was studied by Allen and Stiles (1981), in which 161 drugs were tested on
EMIT-dau® screens for opiates, amphetamines, barbiturates, benzodiazepines, methadone,
propoxyphene and cocaine metabolite. Of these 161 prescription and OTC products, 65 caused some
false positives to occur, with some of these drugs provoking false positives in as many as four of the seven
EMIT® tests. Most of these positives occurred at concentrations of the tested drug that are not achievable
in human urine and are not practical problems. However, they do illustrate the issue of cross-reactivity (or
enzyme disruption) and should indicate that future chemical variants may be reactive. Only the cocaine
screening test, which depends on detection of the cocaine metabolite benzoylecgonine, was completely
free of cross-reactivity. However, the methadone screen was nonspecific enough so that many compounds
showed cross-reactivity. In Table 11, medicinal products are listed from the study by Allen and Stiles that
caused reactions at concentrations in urine of 100 ug/ml or less. Part of the remaining uncertainty about
cross-reactivity exists because studies of cross-reactivity are almost always done by adding pure
compounds, directly to human urine. Most of the drugs listed in Table II do not reach concentrations of 100
ug/ml in usual human use. However, the tests should be done on humans consuming the drug, because
such studies would examine the neglected possibility that metabolites of chemicals contribute importantly
to cross-reactivity. Many of the EMIT® antibodies (e.g., opiates, benzodiazepines and propoxyphene)
react to human metabolites of the primary compounds.

In Table III, all cross-reactants found in the literature resultant from both the addition of drugs to human
urine and studies of humans taking the compounds are compiled. These are compared to the cross-
reactants listed in the Syva Corporation literature supplied to the author on request from the company.

Reactions Due to Human Enzymes

Of the enzymes utilized by EMIT®, both lysozyme and malate dehydrogenase appear in human urine
(Arcenal & Osterloh 1982; O'Connor & Regent 1981). Alcohol dehydrogenase and G6PDH ordinarily do
not.

A false-positive test could occur in some individuals because they excrete unusually large amounts of
endogenous lysozyme or malate dehydrogenase. Because of this problem, a blank should be run with all
positive tests employing either of these two enzymes. This is stated in the Syva Corporation brochures for
the pertinent EMIT-dau® tests, but is omitted in the EMIT-st® cannabis booklet. It is also not shown in a
booklet that depicts in a pictorial fashion the ease of doing the cannabis tests (Syva Corporation 1982).
These points are not made to accuse Syva Corporation of ignoring the problem, but of a certain
indifference in the face of selling the kits to be used by personnel not primarily trained in laboratory
techniques. This author has informally and nonsystematically asked on-site users of the cannabinoid
EMIT-st® method if they were cautioned to run blanks, and received only negative answers.

The lysozyme problem may be greater than initially stated. A recent article by Arcenal and Osterloh (1982)
noted the appearance of lysozyme at levels high enough to interfere in 10 percent of samples run at one
laboratory. The article also described a failure to find an easy resolution of the problem. This was a
hospital-based clinic population and high urinary lysozyme may have reflected a higher than usual
incidence of renal disease.

False Positives (or Unconfirmed Positives) in the Real World

A careful, skilled laboratory, one may assume, will have minimal operator error, will run blanks on all
positives and will anticipate common cross-reactants. Despite this, a number of studies (none done on-
site) reported false positives (see below). In this literature, reports of a percentage of false positives
referred to the percentage of positive EMIT® tests that were not confirmed by alternate tests. A 10 percent
false-positive rate does not mean that of all people tested, 10 percent yielded false tests. Rather, a 10
percent false-positive test rate means that of those found positive, 10 percent could not be confirmed.
These cited studies were seldom critical of EMIT®. In fact, most contained favorable opinions.

A survey of urines from drug abuse treatment programs reported that 10 percent of EMIT® positive tests
were unconfirmed by TLC and in a focused study of barbiturates, a 9.7 percent false-positive rate emerged
(Oellerich, Kulpmann & Haechel 1977). In a study by Fletcher (1981), 26 subjects required to submit
urines because of forensic cases (usually auto accidents) underwent EMIT® urine tests. There emerged a
total of 22 unconfirmed positives (five for amphetamine, seven for benzodiazepines, six for opiates and
four for propoxyphene). This study truly reported some unconfirmed positives because, at times, EMIT®
was the sole test. Fenton and colleagues (1980) identified a 6.6 percent false-positive rate for
benzodiazepines. In an early study by Mule, Bastos and Jukofsky (1974), urines from a series of New York
State drug abuse treatment programs provoked false positives: 8.7 percent false positives for morphine;
2.6 percent false positives for methadone; 5.6 percent false positives for opiates; 12.5 percent false
positives for amphetamine; 5.1 percent false positives for barbiturates; and 10.0 percent false positives for
cocaine. The authors of the article logically enough state that "...additional analysis must be performed to
confirm the presence of drug in biological material after a positive result...."

The issue of independent confirmation already mentioned is critical. A positive test by EMIT® or other
method used for primary screening should be confirmed by an alternative analytic method. In fact, RIA or
EMIT® should not back each other. For example, the morphine antibody used in the Roche Abuscreen®
RIA is close in structure to the EMIT® antibody (Willette 1984). There are a variety of arguments around
this issue growing out of the experience of the U.S. military (to be discussed below). Many commentators
now feel that a positive immunoassay screen must be confirmed by gas chromatography plus mass
spectrometry (GC/MS). This may be particularly applicable when an accused individual brings suit after
losing job or status privileges.

Military Screening Programs

One should not be surprised that a military command structure would decide that mass screening of
enlisted personnel for drugs would be a desirable tool. Although much of this article has discussed the
EMIT® test, it has a relatively minor role in the following story. The problems of laboratory performance,
faulty confirmation, legal action and carelessness do.

In February 1984, Lieutenant Colonel Michael Clarke announced that the Army and the Air Force were
reviewing the results of 100,000 urinary drug tests administered between April 1982 and November 1983.
An American Civil Liberties spokesperson estimated that as many as 30,000 military personnel might be
eligible to have disciplinary action against them dismissed.

The Navy had experienced similar problems. In 1982, the Navy began a massive urinary surveillance
program. Naval laboratories increased their activities from 800 tests per month to 10,000 tests per month
in each of four laboratories. By July 1982, a number of naval commanders began questioning the frequent
occurrence of positive specimens. Six thousand (6,000) positive urines reported between January and
September 1982 were reexamined. Of these 6,000 samples, some 2,000 could not, according to the Navy
publication All Hands (Unsigned 1983), "be scientifically substantiated as positive." Another 2,000 samples
were missing some form of documentation. This author has not learned whether these failures were in
terms of chain of custody, handling of data, operator error, failure to confirm false positives or some
combination thereof. Lieutenant Commander Deborah Burnette, a Navy spokesperson, stated that
sometimes the same test was used for both the finding and confirmation. In another interview with
Burnette, it appeared that she was referring to the fact that at least one of the Navy labs used EMIT® as a
back-up test to RIA. The Navy subsequently announced that it will not use EMIT® in this fashion again.
The Navy is the only important current military user of EMIT®, where it is chiefly employed on site on ships
at sea.

The Army had stopped using Navy labs in 1982 because a number of Army personnel (probably 1,200)
had been affected by these Navy laboratory problems. However, the Navy's 1982 problems had apparently
been paralleled by errors at the Army's Fort Meade tab. Problems at this lab emerged when a civilian
lawyer aggressively defended soldiers disciplined on the basis of reports indicating marijuana use. (All
Army and Air Force primary screens for marijuana use utilize RIA.) Because these men refused offered
administrative punishment, they were subject to court-martial. They were then entitled to a defense that
demanded that the lab records be examined by civilian experts. Many court-martials depending on these
records were then dropped.
These events led to the appointment of an investigative commission under the leadership of Major General
David Einsel, a deputy assistant to the Secretary of Defense. This commission utilized civilian consultant
toxicologists. The commission was later criticized by a nonconsultant civilian toxicologist, Arthur McBay,
who once had been a Navy consultant. McBay objected to the fact that civilian consultant Dr. Robert
Willette was at the time a consultant to the Navy Military Personnel Command and Dr. Mahmond A.
Elsohly worked in the late 1970's for Dr. Carlton Turner. McBay feared this biased their views in favor of
drug testing methods currently in use by the military.

The Einsel Commission Report was partially presented in December 1983 at a White House meeting, but
was not fully reported until March 1984. It reported a devastating error rate and stated that the following
percentages of positive tests at four major facilities (i.e., Fort Meade, 97 percent; Brooks, 60 percent;
Wiesbaden, 75 percent; Tripler, 20 percent) from April 1982 to November 1983 demonstrated "a basis for
argumentation as to legal or technical credibility or sufficiency." The Commission Report stated that many
problems were now solved.

For reference, the Army and Air Force were performing approximately 800,000 tests per year at these
facilities and in the 20 months approximately 1,320,000 tests had been performed. The rate of positive
reports was approximately 10 to 12 percent. This probably explains the 100,000 figure given as the
number needing review in an earlier estimate.

The Einsel Commission Report also indicated that most errors were not related to the tests themselves but
to poor management, inadequate personnel, broken chain of custody, and faulty maintenance and
transmission of reports and records. Einsel maintained that his commission found "no false positives." This
statement seems untenable. A former commander of the Brooks lab estimated a false-positive rate of
three to five percent based primarily on contamination of glassware with positive urine. Two civilian
toxicologists were given 60 positive reports from Fort Meade for review and they identified five positive
screening tests that were subsequently found to be negative on a confirming test. A final criticism of the
Einsel Commission Report occurred because of its recommendation that screening tests be confirmed by
GC. Some critics felt that the confirmation should include GC/MS because a number of GC-alone
confirmations were reported to be inaccurate. These annual screening tests now include probably 13
million RIA screens in nine laboratories: Navy (5), Army (3) and Air Force (1). The Navy continues to use
at least 30,000 EMIT® tests per month.

Laboratory Quality Control

Mass urinary screening is a difficult business. The immunoassay tests that are extremely valuable and
impressive tools in some settings may not have performed so well in mass screening settings. Some of the
difficulties reside in the imperfect nature of the technology and some reside in the imperfect nature of the
operator. Indeed, one can imagine the astonishingly boring work of handling thousands of specimens with
only an occasional positive result to excite, which may be potentially false.

This article has not concentrated on EMIT® because it is a particularly bad test, but because its sellers
apparently wish to place it on site at many American industries. What reason does one have to believe that
these relatively undertrained personnel will do well even if the fears raised about cross-reactivity and
urinary lysozyme are overemphasized? The answer is very little if the few reports are true that assessed
the competence of clinical labs that are not on site.

According to Lundberg (1972), "The performance of even the 'best' toxicology laboratories on urine drug
screens is grossly detective, with frequent false positives and false-negative results and misidentifications."
Lundberg cited other studies (Sine & Murray 1972; Fujimoto & Wang 1970) and an unpublished survey by
the California Association of Toxicologists. in this latter survey, he cited a 20 to 70 percent error on
unknown samples, describing unpublished data gathered by state corrections' officials.

In a later paper, Dinovo and Gottschalk (1976) surveyed the competence of nine laboratories to assess
unknown samples in both urine and a solution of human albumin. They found that "the results for the
proficiency samples point out startling interlaboratory differences in accuracy and precision of detection of
drugs." Their report chiefly described false negatives. Only two of nine laboratories associated with
coroners' offices identified and quantified all of the six unknown drugs. There were 18 failures to find drugs
in 54 opportunities. Another group of laboratories consisting of forensic, commercial and clinical facilities
did not fare any better, with 31 failures out of 95 possible findings. Six of the 19 labs identified drugs that
were not there.

EMIT® Cannaboid Tests in the Field

A critical problem in assessing EMIT® as to overall performance and suitability is the absence of
interpretable field tests. The Syva Corporation product literature essentially always refers to in vitro
laboratory testing to confirm that the test is both reliable and accurate. The procedure is very clearly
described by Syva Corporation scientists (DeLaurentis et al. 1982) in a NIDA research monograph. After
carefully explaining the EMIT® method, a technique of confirmation is described and depicted. Normal
urine not containing marijuana metabolites was tested by EMIT® and compared with the same urine to
which 50 ng/ml of 11-nor-delta-9-tetrahydrocannabinol-carboxylic acid (delta-9-THC-acid) had been
added. The display showed precise separation between normal and the same normal, but spiked, urine.
This same display depicted in the NIDA research monograph (see Figure 4) is used in the Syva
Corporation product literature. It is distressing that the amount of delta-9-THC-acid was never quantified,
but was always presented as the percentage of urine versus "separation units" or "assay response rate."
This author cannot easily interpret such units and wonders if the overlap between normal and spiked urine
would be more prominent if it was displayed in quantitative terms.

In the introduction to this paper, a polygraph study done under field conditions was referred to. It is not
unreasonable to ask for the evaluation of EMIT® under field conditions, but there are relatively few such
studies. Three evaluations of EMIT® in the field were located. Although all three have problems, they
should be placed against the in vitro evaluations of spiked urine samples. Indeed, field evaluations are
always problematical. Specimens may not be ideally collected or handled. Subjects may present urine
containing an interfering drug or drug metabolite, or they may have renal tubular disease increasing the
amount of lysozyme or malate dehydrogenase in the urine. Field technicians may not be aware of these
problems and the rate of operator error may be high. None of these field studies evaluated the most
important variable, the briefly trained workers who are to be the on-site operators. Despite these warnings,
all who are interested in these issues should want to know how EMIT® performs under field conditions. All
three evaluations described below are evaluations of the EMIT® cannabinoid test and some important
methodological and pharmacological issues will again be briefly reviewed.

The EMIT® cannabinoid systems use an antibody prepared to the tetrahydrocannabinoid metabolite delta-
9-THC-acid. The metabolite is covalently linked to a pig heart malate dehydrogenase, which is inactivated
by the binding of the antibody. The detection system utilizes a spectrophotometer, which detects
conversion of the coenzyme nicotinamide adenine dinucleotide to its reduced form, nicotinamide adenine
dinucleotide hydrogenase. All three field trials used GC/MS as a confirmational test, sometimes with other
tests as well.

Center for Human Toxicology Trial

In 1982, the NIDA research monograph on analysis of cannabinoids in biological fluids contained a field
evaluation of the EMIT® cannabinoid test conducted by the Center for Human Toxicology (CHT) at the
University of Utah (Peat, Finkle & Deyman 1982). Briefly, the CHT coordinated the confirmation of EMIT®
positive urines for delta-9-THC-acid mailed to them from 12 cooperating analytical labs. Most specimens
had been obtained from auto accident casualties, but others originated from emergency room admissions.
These positive specimens were sent to a single test sight for confirmation. In addition to the samples from
cooperating laboratories, the CHT itself assessed a number of specimens and compiled a separate listing
for those. The performance of EMIT® was disappointing. For the 12 laboratories, the rate of unconfirmed
positives was 11 percent. The CHT nonconfirmation rate was much higher. Of 98 EMIT® positive samples,
37 were unconfirmed by GC/MS: a 38 percent false-positive rate. However, an important technical problem
clouded the issue. During the evaluation, it became known that most delta-9-THC-acid in the urine is
conjugated to glucuronide (Williams & Moffat 1980). The GC/MS method had been developed for free
delta-9-THC-acid. This information became available too late to recheck all specimens after a hydrolysis
step to convert bound material to free. Some unknown percentage of samples had in fact been hydrolyzed.
A few specimens were analyzed both before and after hydrolysis. In almost every instance, the hydrolysis
did increase the amount of delta-9-THC-acid measured by GC/MS, but some still remained negative and
unconfirmed after hydrolysis. The authors and later commentators believed that this technical problem
explained "the poor correlation between the EMIT values and those obtained by GC/MS." There has never
been a published attempt of which this author is aware to replicate the study and it has never been
confirmed that the hydrolysis is of critical importance.

The O'Connor-Regent Study

In 1981, O'Connor and Regent published a study in which cannabinoid EMIT® positive urines (submitted
voluntarily and anonymously by college students) were subjected to attempted confirmation by GC/MS. Of
144 positive urines, the authors sent 60 for confirmation to collaborating laboratories. Overall, only 50 of
the 60 were confirmed: a 17 percent false-positive rate. Twenty-four (24) of 30 specimens were confirmed
by GC/MS. Seventeen (17) of 20 other specimens were confirmed by GC/MS after hydrolysis. This
Indicates that even with hydrolysis before GC/MS, the false-positive rate was 15 percent. It seems clear
that hydrolysis does not solve the problems. It also seems clear from reading the study that careful
laboratory efforts, including the running of blanks to rule out endogenous urinary malate dehydrogenase,
were observed.

New Jersey Department of Corrections

In recent years, a number of court cases have been heard in which inmates of a state correctional system
have brought suit to protest the use (apparently widespread) of a single unconfirmed EMIT® test to bring
about disciplinary action against inmates. In New Jersey, as in a previous Massachusetts case, the court
decided that such action was inappropriate and the state was ordered to cease such activity.1

In preparation for this case, the Department of Corrections sent 400 EMIT® positive cannabinoid tests on
inmates to the Roche Clinical Laboratories in Raritan, New Jersey. Of these, 107 were unconfirmed by
RIA, an inappropriate confirming test. These same 107 tests were sent to Roche Analytic Laboratories in
Richmond, Virginia, where all were unconfirmed by GC/MS (after hydrolysis). This constitutes a 1984 field
trial of EMIT® cannabinoid tests in which the false-positive rate exceeded 25 percent. The EMIT® tests
were run by a trained laboratory technician employed in a state laboratory. These data were not presented
in the court hearing. The state agreed to submit to the order and agreed to use confirmation tests on all
EMIT® positives without argument.2

Conclusions

XIV. a. Table I. Drug Detection Limits (SYVA Corporation 1982

XIV. b. Table II. Cross-Reactivity With EMIT® Test at 100 (G/ML or Less) (ALLEN & STILES 1981)
XIV. c. Table III. Cross-Reactants

Technology traps people and they begin to serve the technology more committedly than it serves them.
Such entrapment is aided by a refusal to be critical in the face of flawed technological approaches.
Demystifying the testing and focusing on the real world performance slows such entrapment.

The Syva Corporation wishes to supply on-site EMIT® for relatively untrained personnel to engage in
difficult biochemical manipulations. There are no data confirming that such personnel can do this work
adequately and the EMIT® test has consistently failed field condition analysis. This author is convinced
that such use of EMIT® is improper.

XIV. a. Table I.
Drug Detection Limits (SYVA Corperation 1982)

Detection
Drug
Limit
morphine 0.5 ug/ml>
methadone 0.5 ug/ml>
amphetamine 2.0 ug/ml>
secobarbital 2.0 ug/ml>
benzoylecgonine 1.6 ug/ml>
oxazepam 0.7 ug/ml>
propoxyphene 2.0 ug/ml>

XIV. b. Table II.

Cross-Reactivity With EMIT® Test at 100 (G/ML or Less) (ALLEN & STILES 1981)

Generic and Brand

EMIT® Test
Names
Am Ba Be Co Me Op Pr
amitriptyline Hcl (Elavil®) X
carisoprodol (Soma®) X
clindinium bromide
X
(Quarzan®)
cloxacillin Na (Tegopen®) X
diphenhydramine Hcl
X
(Benadryl®)
ethoheptazine citrate
X
(Zactane®)*
imipramine Hcl (Tofranil®) X
isoxuprine Hcl
X
(Vasodilan®)
orphenadrine citrate
X
(Norflex®)
perphenazine (Trilafon®) X
promethazine HCl
X X
(Phenergan®)
thiethylperazine maleate
X
(Torecan®)
tripelennamine Hcl
X X
(Pyribenzamine®)

*No longer marketed in the United States

Am=amphetamine
Ba=barbiturate
Be=benzodiazepine
Co=cocaine
Me=methadone
Op=opiate
Pr=propoxphene

XIV. c. Table III.

Cross-Reactants

From Medical
Literature
(Hausmann et al.
1983; Svenneby,
From Syva Corporation
Wedege &
Product Literature
Karlsen 1983;
Allen & Stilles
1981; Budd
1981a, 1981b)
Amphetamine
methamphetamine clortermine
phentermine benzphetamone
mephentermine phenmetrazine
ephedrine indomethacin
nylidrin tranylcypromine
phenylpropanolamine tuaminoheptane
isoxuprine
Benzodiazepine (Oxazepam)
chlordiazepoxide clindinium
diazepam cloxacillin
flurazepam tripelennamine
lorazepam temazepam
N-desalkylflurazepam halazepam
N-desmethyldiazepam nitrazepam
flunitrazepam
clonazepam
chlorazepate
Opiate
morphine pholocodine
codeine dosylamine
hydromorphone ethoheptazine
nalorphine promethazine
meperidine
oxycodone

(Top)

Notes

1. Denike v. Fauver (U.S. District Court for New Jersey, May 14, 1984; D..J. Debvoise, U.S. District
Judge).

2. This author is grateful to the New Jersey Department of Corrections for permission to publish this data.
They state that the current nonconfirmation rate is much lower.

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Copyrighted material. Reprinted by permission.