Results - continued

ruleline

Objective Measures of Drug Use

Summary

As noted earlier, 639 oral fluid samples were analyzed for drugs. Though 642 oral fluid samples were collected, 3 containers leaked during transport and sufficient volume to conduct analyses was available only for the remaining 639. Of these 639, there were also 394 blood samples available for analysis. Blood samples were provided by 406 subjects; however, 12 were unable to provide sufficient volume to permit analysis. Every subject who provided a blood sample also provided an oral fluid sample.

Drugs were detected in 96 cases:

  • 33 paired samples (34.4%) were positive via oral fluid and blood
  • 28 (29.2%) were positive via oral fluid where blood was refused
  • 29 (30.2%) were positive via blood only
  • 6 (6.2%) were positive via oral fluid only

In the subjects where blood only was positive for therapeutic drugs, the concentrations detected were all in the therapeutic range and would not be considered at a high enough level to cause impairment. 

Drugs known to cause impairment were detected in many of the specimens and included marijuana, benzodiazepines (diazepam, alprazolam), carisoprodol, the narcotics (oxycodone, codeine, hydrocodone), methadone, tramadol, and cocaine. 

Antidepressants

The antidepressants/selective serotonin uptake inhibitors (SSRIs) such as fluoxetine and sertraline can cause impairment in rare circumstances where extremely high blood concentrations are measured.  The data reviewed does not suggest that the concentrations found would have a significant effect on one’s ability to operate a motor vehicle. Fluoxetine and its metabolite norfluoxetine were found in four blood samples with corresponding oral fluid negative samples; and in four paired samples. Sertraline was found in five blood samples with correspondingly negative oral fluid specimens; and in five pairs of samples both were positive for the drug.

Benzodiazepines

Benzodiazepines are known to cause impairment in traffic cases when present at high level. There were four cases in which alprazolam was reported, however, in two of the subjects, the concentrations were so low (1 ng/mL and 4 ng/mL) it is highly unlikely that the direct pharmacological effects of the drug would cause impairment.  In the other two cases (27 ng/mL and 19 ng/mL in the presence of THC), while the concentrations were within the therapeutic concentration range, it should be noted that the desired/therapeutic effect of alprazolam is sedation - which would have a detrimental effect on driving a motor vehicle.

In both of these subjects, corresponding oral fluid analysis did not detect alprazolam and it is likely that the cross-reactivity on immunoassay tests for alprazolam is low.  However, it is known that benzodiazepines do not appear in the oral fluid in very high quantity due to their high level of protein binding.

The most common benzodiazepine, diazepam (Valium™) and/or its metabolites nordiazepam, oxazepam and temazepam were detected in 4 blood samples and not in the corresponding oral fluid specimens.   Diazepam and nordiazepam were found in one oral fluid sample, the corresponding blood sample was refused.

Carisoprodol

In one case, carisoprodol (Soma™) and its metabolite meprobamate were detected in both blood and oral fluid. Even at therapeutic concentrations, this may cause driving impairment as the desired effect is sedation.

Marijuana

The most prevalent drug detected was marijuana. There appeared to be a strong positive correlation between the oral fluid and blood tests, the only discrepancies (negative oral fluid and a positive blood) are from 10 cases where the inactive metabolites were detected in blood, and not the active tetrahydrocannabinol (THC).

A positive metabolite result (THCA) with a negative parent compound (THC) is consistent with remote use - in these cases a negative oral fluid would not miss an impaired driver.

THC or its metabolites were detected in 37 oral fluid cases and in 23 blood specimens.  Thirteen had corresponding positive oral fluid samples; 10 contained only inactive THC metabolites, as described above. 

In oral fluid, the active parent compound, tetrahydrocannabinol (THC) was detected in all cases where marijuana use was determined.  In 22 samples where THC was detected in oral fluid, a blood collection was refused.

Cocaine

Cocaine or its metabolites were detected in 14 oral fluid samples and only 4 blood samples, hence oral fluid appears to be a better specimen type for the detection of recent cocaine use. Of the other 10 oral fluid positive samples, 5 had corresponding blood samples which were negative, and 5 subjects refused to give blood.

There was only one blood sample containing parent cocaine, whereas oral fluid detected 13 positives. The presence of parent drug, (cocaine) in either specimen indicated the presence of active drug in the system.

Other Stimulants

Methamphetamine, amphetamine, pseudoephedrine, phenylpropanolamine and phentermine are members of the same sympathomimetic stimulant group of drugs. They were detected in a small number of cases.

Other Drugs

The other drugs detected (butalbital, amitryptiline) were only present in one or two cases, and given the reported concentrations, none at a concentration to cause impairment. Overall:

  • oral fluid specimen collection compliance was considerably better than blood
  • oral fluid accounted for more total drug positives than blood 
  • there were significantly more positive results for the impairing drugs cocaine and THC in oral fluid compared to blood
  • low saliva:plasma ratio continues to cause difficulty in oral fluid detection of benzodiazepines

Table 30 presents each of the drug positive results for both oral fluid and blood, and Table 31 summarizes those results.

Table 30. Specimens Positive for Drugs*

Specimen ID

Oral Fluid

Blood

1

Negative

THC-COOH 5

2

Negative

 Sertraline 31

3

Negative

Alprazolam 1

4

Negative

Alprazolam 4

5

Negative

Diazepam 15; Nordiazepam 9

6

Negative

Diazepam 582, Nordiazepam 881, Oxazepam 140, Temazepam 31

7

Negative

Fluoxetine 14; Norfluoxetine 13

8

Negative

Fluoxetine 17; Norfluoxetine 14

9

Negative

Oxycodone 10; Pseudoephedrine 87

10

Negative

Oxycodone 7

11

Negative

Sertraline 19

12

Negative

Fluoxetine 88, NorFluoxetine 178

13

Negative

Phentermine 19 ; THC-COOH 14

14

Negative

Pseudoephedrine 340; Phenylpropanolamine 16

15

Negative

Pseudoephedrine 46

16

Negative

Alprazolam 27

17

Negative

Hydrocodone 11

18

Negative

Pseudoephedrine 19

19

Negative

Pseudoephedrine 19

20

Negative

Pseudoephedrine 160; Phenylpropanolamine 12

21

Negative

THC-COOH 17

22

Negative

THC-COOH 18

23

Negative

THC-COOH 9

24

Negative

THC-COOH 11

25

Negative

THC-COOH 12; Sertraline 158

26

Negative

THC-COOH 26

27

Negative

Fluoxetine 39; Norfluoxetine 40

28

Negative

Sertraline 17

29

Negative

THC-COOH 5

30

Amitriptyline 23; Nortriptyline 12

Amitryptyline 15; Nortriptyline 6 

31

Amphetamine 23, Methamphetamine 37

Negative

32

Amphetamine 122

Amphetamine 48

33

Butalbital 446; Codeine 86

Refused

34

Butalbital 456

Refused

35

BZE 3.5;  COC 12.1

Refused

36

BZE 56

Negative

37

Carisoprodol 18; Meprobamate >1000

Carisoprodol 100; Meprobamate 2000

38

COC > 1000 ; BZE >1000; THC 11

Refused

39

COC > 500; BZE 303

COC 54; BZE 132; Cocaethylene 10

40

COC 22; BZE 20

BZE 65

41

COC 23; BZE 97

BZE 157; THC-COOH 29

42

COC 4

Negative

43

COC 87; BZE 19

Negative

44

COC 9.4

Negative

45

COC 9; BZE 3

Negative

46

Fluoxetine 35

Fluoxetine 71; Norfluoxetine 148

47

Fluoxetine 40, THC 82

Fluoxetine 36; Norfluoxetine 89

48

Fluoxetine 51; Norfluoxetine 55

Fluoxetine 54; Norfluoxetine 99

49

Fluoxetine 71

Fluoxetine 211; Norfluoxetine 169

50

Hydrocodone 20, Oxycodone 4

Hydrocodone 14

51

Hydrocodone 36

Refused

52

Hydrocodone 88

Hydrocodone 7

53

Methadone > 1000

Refused

54

Methamp 677, Amp 71, THC 420

Refused

55

Methamphetamine 4876; Amphetamine 541

Methamphetamine 942; Amphetamine 117

56

Nordiazepam 9; Diazepam 8

Refused

57

Phentermine > 100; THC 1.3

Phentermine 129

58

Pseudoephedrine > 100; THC 72.6

Pseudoephedrine 50; THC 2; OH-THC 0.8; THC-COOH 30

59

Sertraline 18.4

Sertraline 79; Diazepam 34, Nordiazepam 45, Oxazepam 8

60

Sertraline 22

Sertraline 18

61

Sertraline 24

Sertraline 112

62

Sertraline 62

Sertraline 203

63

 THC 6.6

Refused

64

THC > 100

Refused

65

THC > 100

THC 3.8; 11-OH-THC 1.2; THC-COOH 144

66

THC > 400

Refused

67

THC > 500

THC 27; 11-OH-THC 13; THC-COOH 247

68

THC 0.9

Refused

69

THC 1.3

THC 1.4; 11-OH-THC 1; THC-COOH 89

70

THC 1.7

THC-COOH 12

71

THC 10.6

THC 0.5; 11-OH-THC 0.6; THC-COOH 29

72

THC 10.6

Refused

73

THC 10.8

Refused

74

THC 11.5; Meth >500, AMP >500

Methamp 175; Amp 59; THC-COOH 29

75

THC 13.7

Refused

76

THC 14.1; COC 8; BZE 25

Refused

77

THC 15.6

Refused

78

THC 168; COC 9

Refused

79

THC 19

Refused

80

THC 2.3

Refused

81

THC 21.2

THC 0.8; THC-COOH 41

82

THC 21.2; COC 75, BZE 10

BZE 104; THC 3.8; 11-OH-THC 2.2; THC-COOH 209

83

THC 23.4; Sertraline 8

THC 1.6; 11-OH-THC 0.6; THC-COOH 61; Sertraline 17

84

THC 24.7

Refused

85

THC 3.8

THC 0.5; THC-COOH 13

86

THC 37.9

Refused

87

THC 4.4

Refused

88

THC 53.9; COC >500; BZE 422

Refused

89

THC 6.7

Refused

90

THC 62.2

Refused

91

THC 65

Refused

92

THC 7.4

Refused

93

THC 7.8

THC 0.8; THC-COOH 31

94

THC 9.8

Alprazolam 19, THC 3.6; 11-OH-THC 6.1; THC-COOH 124

95

Tramadol 160.4

Diazepam 6, Tramadol 19; Desmethyltramadol 28,  Sertraline 32 

96

Tramadol 1724

Tramadol 130; Desmethyltramadol 22

Table 31. Summary of Total Drug Positive Results by Matrix Tested

Color Key

Both Oral Fluid & Blood Positive

33

Oral Fluid Positive

6

Blood Positive

29

Oral Fluid Positive; Blood Refused

28

Total

96

In Table 32, the overall results for drug positives are summarized by drug and sample type.

Table 32. Overall Drug Results (Includes Specimens Positive for Multiple Drugs)

Drug Class

Positive Samples

Oral Fluid

Blood

Amitriptyline/nortriptyline

1

1

Amphetamine/methamphetamine

4

3

Barbiturates

2

0

Benzodiazepines

1

6

Carisoprodol/meprobamate

1

1

Cocaine and metabolites

14

1

Fluoxetine

4

8

Methadone

1

0

Opiates (hydrocodone, oxycodone, codeine)

4

4

Pseudoephedrine/phentermine/phenylpropanolamine

2

8

Sertraline

5

9

THC

37

20

Tramadol

2

2

Total

78

66

In Table 33, we summarize the combined results of the oral fluid and blood tests for drugs other than alcohol. Successful laboratory analyses were conducted on 639 drivers. Oral fluid was analyzed for all of these drivers and blood for 394 of them. All drivers who provided blood also provided oral fluid. Thus, 14 of these 639 drivers, or 2.2 percent tested positive for cocaine. The most frequently encountered drug was cannabinoids, with 47 or 7.4 percent of drivers having THC or a metabolite of that substance on board. One must bear in mind that metabolites of THC appear in blood well after the active phase of its potentially impairing effect.  Cannabinoids were followed in frequency of appearance by two stimulants, cocaine and amphetamines, each of which presented 2.2 percent of the time in tested drivers. Benzodiazepines (Valium and its relatives) 1.6 percent, Sertraline (Zoloft) 1.6 percent, Fluoxetine (Prozac) 1.3 percent were the next most frequently encountered drugs. Opiates were encountered in 1.1 percent of the tested drivers. Other drugs appeared much less frequently. As indicated in Table 33, many drivers tested positive for more than one drug. Thus we provide as the last line of this table the number of drivers who tested positive for any drug, 96. This constitutes 15.0 percent of the total group who provided oral fluid or oral fluid and blood.

Table 33. Drivers Testing Positive for Drugs other than Alcohol in either Oral Fluid or Blood

Drug

N

% (Out of Valid Drug Tests = 639)

Cocaine

14

2.2%

Opiates

7

1.1%

Amphetamines

14

2.2%

Cannabanoids

47

7.4%

Benzodiazepines

10

1.6%

Barbiturates

2

0.3%

Methadone

1

0.2%

Tramadol

2

0.3%

Sertraline

10

1.6%

Fluoxetine

8

1.3%

Tricyclic Antidepressants

1

0.2%

Carisoprodol

1

0.2%

Driver tested positive for any of above drugs

96

15.0%

Ethanol

The results for ethanol are given in Tables 34 and 35. Some specimens correlate well between the breath, oral fluid, and blood samples, while others are difficult to explain.

Saliva has been shown to equilibrate rapidly with blood in terms of its alcohol content, being slightly higher on average than whole blood.  Saliva/whole blood ethanol concentration ratios have been reported on average to be 1.08 for male subjects (n=48) within the first six hours after drinking (range: 0.84-1.36) (Jones, 1979). Other studies have reported similar ratios:

  • 1.10 (n=13; range 0.97-1.31) (Jones, 1993)
  • 1.20+/-0.13 (n=6; range 1.10-1.40) (Ferrara et al., 1994)
  • 1.12 (n=244])and 1.10 (n=21) (Haeckel & Bucklitsch, 1987)

On the whole, the data appear to correlate well with the paired blood/breath, with some outliers.  There were three cases where breath was negative, yet blood was positive at .03, .04 and .08 (oral fluid negative in all these cases).
In seven subjects, the breath was negative, and oral fluid was positive between .02 and .28. In these seven cases, blood was refused four times, and three paired breath and blood samples were negative.  Such discrepancies are difficult to explain, as breath/blood correlation in particular is widely studied.

Issues

These discrepancies could be related to possible collection issues particularly for oral fluid. In the early part of the study, the volatility of ethanol was not addressed.  In the later location collections, the specimens were frozen as soon as possible after collection, and sent to the laboratory on dry ice. At the laboratory, improved sampling processes were implemented involving recapping and freezing the specimens as soon as sufficient sample volume was removed for testing.  In this way, the loss of ethanol was minimized and correlation between the breath/blood and oral fluid improved as the study progressed.

When oral fluid is collected, the swab is placed into a transportation buffer; the device is capped, and sent to the laboratory for testing. The volume of the transportation buffer is 3 mL, therefore when one milliliter (1 mL) of saliva is placed into the tube, the total amount of sample volume for testing is 4 mL, and the drug and ethanol content in the sample is diluted by four. In the ethanol testing, it is possible when correcting for the dilution, a value below the limit of quantitation (LOQ) of the assay was multiplied by four, to give the final result. At the low end of the range (.005–.02), the correlation to the breath test was 17.3 percent; in the range above .02, the correlation to the breath test improved to 35/87 = 40.2 percent. This was also true with the blood samples, with 8.6 percent correlation at the low end of the testing range, improving to 19/87 (21.8%) above .02.

Table 34 presents, for those subjects who were positive for any alcohol in any matrix, the results for breath alcohol (%), oral fluid ethanol (%), and blood ethanol (%). Table 35 summarizes those data.

Table 34. Specimens Positive for Ethanol in at Least One Matrix

Breath Alcohol (%)

Oral Fluid Ethanol (%)

Blood Ethanol (%)

0

0

.03

0

0

.04

0

0

.08

0

.02

0

0

.02

0

0

.04

Refused

0

.05

Refused

0

.09

Refused

0

.16

0

0

.28

Refused

.005

0

0

.005

Refused

Refused

.006

0

0

.007

0

0

.008

0

Refused

.008

0

Refused

.009

0

0

.011

0

Refused

.012

0

0

.012

0

Refused

.012

.02

Refused

.013

0

0

.013

0

Refused

.014

0

0

.014

.03

Refused

.015

.05

0.14

.016

Refused

Refused

.017

Refused

Refused

.018

0

0

.018

0

Refused

.019

0

.03

.019

.03

Refused

.019

Refused

Refused

.02

0

0

.02

Refused

Refused

.021

0

0

.021

0

Refused

.021

0

Refused

.022

0

0

.022

0

Refused

.023

.05

0

.024

0

0

.024

.03

0

.024

.03

Refused

.025

0

0

.025

.03

Refused

.025

.10

.08

.026

0

.03

.026

.05

Refused

.027

0

Refused

.028

.02

Refused

.029

0

0

.03

.03

.04

.03

Refused

Refused

.03

Refused

Refused

.032

.09

0

.033

Refused

Refused

.033

Refused

Refused

.034

0

0

.034

0

.03

.035

.07

.06

.036

0

Refused

.037

.06

.07

.037

Refused

Refused

.038

0.04

Refused

.039

0

Refused

.039

0

Refused

.039

.06

.04

.039

.06

Refused

.039

.06

Refused

.041

0

Refused

.041

Refused

Refused

.043

0

Refused

.044

0

Refused

.044

.07

.06

.045

Refused

Refused

.05

0

.05

.052

.07

Refused

.052

0.1

.06

.052

Refused

Refused

.052

Refused

Refused

.053

.05

.05

.053

Refused

Refused

.056

Refused

Refused

.058

.04

.07

.059

0

0

.059

.07

Refused

.062

Refused

Refused

.064

0

.09

.065

0

.10

.066

0

0

.067

.03

Refused

.067

.13

Refused

.069

Refused

Refused

.072

Refused

Refused

.074

Refused

Refused

.075

0

Refused

.078

.05

.09

.078

Refused

Refused

.081

.13

Refused

.081

Refused

Refused

.093

0

Refused

.099

Refused

Refused

.103

Refused

Refused

.108

.11

Refused

.11

.11

.17

.112

0

.13

.118

.15

Refused

.122

.09

0.10

.128

.14

Missing

.128

Refused

Refused

.132

.21

Refused

.133

.27

Refused

.134

Refused

Refused

.143

.21

Refused

.146

Refused

Refused

.15

Refused

Refused

.15

Refused

Refused

.154

.07

Refused

.183

.26

.23

N/A

.06

Refused

N/A

.12

Refused

Table 35. Specimens Positive for Ethanol in at Least One Matrix

Breath Result

# Breath Samples

Oral Fluid

Blood

Positive

Negative

Refused

Positive

Negative

Refused/Missing

N/A

2

2

0

0

0

0

2

0

10

7

3

0

3

3

4

.005–.019

23

4

15

4

2

8

13

.02–.079

66

24

25

17

15

12

39

> .08

21

11

2

8

4

0

17

Total

122

48

45

29

24

23

75

When breath was positive over the legal limit (.08), oral fluid was positive in 11 cases (11/21 = 52.3%); negative in 2 cases (9.5%) and 8 subjects refused to give a specimen (38%). Blood was positive in 4 cases (4/21 =19%) and subjects refused to give blood in all the other 17 cases.

The total refusal rate for blood was much higher than in oral fluid. From 110 subjects testing positively for alcohol via breath (>0.005), 68 (61.8%) refused to donate a blood sample (one blood sample was missing). In contrast, only 29 (26.4%) refused to give oral fluid.

Fourteen subjects were positive via all matrices (Figure 7).

click for long description

Figure 7. Pattern of BAC Test Results by Biological Matrix

The collection rate for oral fluid was higher than blood. Initial problems with ethanol volatility during collection and storage have been addressed, and correlation between breath and oral fluid results should improve in future studies.

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