Pharmacology & Pharmacy, 2013, 4, 528-534 Published Online October 2013 (
Long-Term Detection of Propofol Glucuronide in Urine
Following Anesthetic Induction and Maintenance with
Joseph Salerno*, Joseph Jones, Mary Jones, Charles Plate, Douglas Lewis
United States Drug Testing Laboratories, Inc. (USDTL), Des Plaines, USA.
Email: *
Received August 7th, 2013; revised September 9th, 2013; accepted September 21st, 2013
Copyright © 2013 Joseph Salerno et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Propofol is the most commonly used compound for the intravenous induction and maintenance of anesthesia. Propofol
addiction and abuse have become causes for concern in the healthcare community, especially among anesthesia and
surgical professionals. The US Drug Enforcement Administration does not list propofol on any Schedules and most
hospitals do not have inventory controls in place to prevent its misuse. Propofol is detectable in blood plasma as the
parent compound for as much as 15 hours post-anesthesia. The metabolite propofol glucuronide (PPFG) has been de-
tected in blood and urine as far out as 60 hours. Here we report the long-term renal excretion of PPFG in specimens
from A) four participants following a 14-day course of orally ingested propofol dosing, and B) a female patient follow-
ing anesthetic induction and 15 minutes’ maintenance with propofol. Urinary PPFG was measurable well above limits
of quantitation up to 6 days following oral ingestion and 28 days post-anesthesia. We also present a third set of data
evaluating the likelihood of passive exposure to aerosolized propofol in the surgical environment by analyzing the lev-
els of urinary PPFG of healthcare workers following operating room work shifts. The results presented here demon-
strate that quantitation of PPFG in urinary samples is an efficient method of long-term screening for propofol misuse
and abuse.
Keywords: Anesthetics; Drug Testing; Metabolism; Pharmacokinetics; Propofol; Propofol Glucuronide; Urine
1. Introduction
Propofol (2,6-diisopropylphenol; Diprivan®, AstraZeneca
Pharmaceuticals) is a fast-acting, short-duration, hypnotic
agent that is administered intravenously for the induction
and maintenance of general anesthesia [1]. With a quick
recovery time following induction and minimal side ef-
fects [2], propofol has become the most widely used com-
pound for intravenously administered general anesthesia
[3]. Propofol rapidly enters the Central Nervous System,
very smoothly induces unconsciousness, and undergoes
swift metabolic clearance [4]. The highly lipophilic na-
ture of propofol results in storage and slow release from
deep tissue depots such as fat deposits and muscle tissues
Although not traditionally seen as a drug of abuse,
non-procedural misuse of propofol by anesthesiology and
surgical healthcare professionals with direct access to the
compound has become a cause for concern [6]. Propofol
abuse among healthcare professionals increased five-fold
from 1997 to 2011, and despite a low incidence of abuse
among anesthesia-based providers (0.10%), the rate of
fatality due to abuse is high (28%) [6]. The fatality ha-
zard of propofol abuse owes in great part to the com-
pound’s extremely narrow window of safety resulting
from the rapid onset of unconsciousness during adminis-
tration. The small difference between a therapeutic dose
and a potentially hazardous dose that can cause acute
respiratory depression creates a very real risk of fatal
overdose if the drug is self-administered [7]. Propofol is
not scheduled with the US Drug Enforcement Admini-
stration and 71% of surveyed anesthesia programs have
no control system in place to secure and account for pro-
pofol supplies [6].
Propofol is metabolized in the liver where it is
*Corresponding author.
Copyright © 2013 SciRes. PP
Long-Term Detection of Propofol Glucuronide in Urine Following
Anesthetic Induction and Maintenance with Propofol
oxidized to 1,4-di-isopropyl quinol, and both propofol
and quinol are subsequently conjugated to glucuronic
acid and excreted in urine [8]. Total body clearance rates
for propofol have generally been seen to exceed hepatic
blood flow indicating other potential routes of clearance
outside the liver [4,8]. Less than 0.3% of the parent
compound is excreted unchangeably [9]. Whether this
disappearance of native propofol in the excreted samples
is indicative of complete metabolic destruction of or
rapid sequestration in deep tissues has not been entirely
characterized. Propofol glucuronide (PPFG) is the pri-
mary metabolite among at least seven major and minor
metabolites, accounting for as much as 62% of recove-
rable conjugated propofol in urine specimens [9].
Post-mortem forensic protocols detect the use of pro-
pofol test for the parent compound in blood samples
[10-14]. However, the brief serum half-life of propofol
(21 - 56 minutes) [15] makes this approach unreliable for
routine substance abuse testing. To our knowledge, the
15-hour profile of propofol in plasma seen by Bleeker et
al. (2008) is the longest window of recovery of the parent
compound reported for blood samples [8]. In the same
report, Bleeker et al. detected urinary PPFG concen-
trations as far out as 60 hours post-anesthesia, suggesting
that testing for propofol use in living subjects is more
easily carried out by measuring PPFG concentrations in
urinary specimens.
Here we report the long-term disappearance profile for
urinary PPFG in specimens collected from a female
patient over a 28-day period following routine procedural
anesthetic induction and maintenance using propofol.
Specimens were assayed for PPFG (ng/mL) by liquid
chromatography tandem mass spectrometry (LC-MS/
MS), and PPFG levels were normalized to 100 mg/dL
creatinine to account for changes in urinary output [16].
In addition, we discuss the findings from two of our
unpublished pilot studies on urinary PPFG clearance, and
the implications of all three datasets on the practice of
routine screening for propofol misuse and abuse.
2. Experimental
2.1. Ethics Statement
The patient who provided specimens for this study is one
of the authors and an employee of United States Drug
Testing Laboratories (USDTL). Specimens provided for
one of our pilot studies were submitted voluntarily by
employees of USDTL. Specimens from the second pilot
study were de-identified aliquots remaining from speci-
mens referred to our lab for routine analysis and con-
sidered waste at the time of assay. Samples from USDTL
employees were voluntarily given, and neither these nor
the waste specimens required an ethics review.
2.2. Subject History and Specimen
Collection-Urinary PPFG Profile Following
Propofol Anesthesia
This study quantified the disappearance of PPFG in the
urine of a female patient following anesthetic induction
and maintenance with propofol during a routine colo-
noscopy examination. The patient was five feet and three
inches tall (1.6 m), 150 lbs. (68 kg), and age 45 - 50 years
old. Propofol was administered intravenously in a total of
250 mL of fluid. A total of 300 mg of propofol was
administered, beginning with a 30 mg induction. Anes-
thesia was maintained for 15 minutes following induction,
and sedation lasted for 25 minutes. Propofol was tolerat-
ed well by the patient.
Thirteen urine specimens 10 mL in volume were
collected from the subject periodically over a period of
28 days. The interval between specimen collections
varied from 1 - 5 days. Urine was collected in 100 mL
polypropylene specimen cups and stored at 2˚C - 8˚C
until tested. The patient’s daily medications, taken orally
prior to specimen collection, included 80 mg acetyl-
salicylic acid (aspirin), 10 mg pravastatin, 1000 mg fish
oil, 10 mg cetirizine hydrochloride, 1500 mg glucosa-
mine, 1250 mg chondroitin-sulfate, and a non-prescrip-
tion multivitamin.
2.3. Subject History and Specimen
Collection-Pilot Study #1: Urinary PPFG
Profile Following Oral Ingestion of Propofol
Pilot study #1 measured the concentration of PPFG in
urine samples taken from four USDTL employees who
had ingested 50 mg of propofol in gel-caps daily for 14
days. Following the 14 day ingestion, 10 mL samples
were collected at irregular intervals as the subjects
needed to void over a six day period, and tested for PPFG.
Urine was collected in 100 mL polypropylene specimen
cups and stored at 2˚C - 8˚C until tested. The participants
consisted of two males and two females between the ages
of 45 - 65 years and ranging in weight from 150 - 300
2.4. Subject History and Specimen
Collection-Pilot Study #2: Urinary PPFG
Resulting from Incidental Exposure
Pilot study #2 utilized de-identified aliquots remaining
from specimens referred to our lab for routine analysis
and considered waste at the time of assay. Personal in-
formation for the donors of these specimens is not avai-
lable. The samples were originally collected from 27 cer-
tified registered nurse anesthetists immediately following
the completion of 8 hour or longer work shifts in
operating rooms where propofol was being administered
Copyright © 2013 SciRes. PP
Long-Term Detection of Propofol Glucuronide in Urine Following
Anesthetic Induction and Maintenance with Propofol
to patients. The purpose of these samples was to test for
PPFG levels in the urine of anesthesia professionals
resulting from incidental exposure to aerosolized pro-
pofol during surgery.
2.5. Chemical Reagents and Materials
DRI® Creatinine-Detect reagent was purchased from
Microgenics Corporation (Fremont, CA, USA). The
internal standard, propofol glucuronide-d17 (PPFG-d17),
was purchased from Toronto Research Chemicals (To-
ronto, ON, Canada). PPFG was purchased from Cerilliant
Corporation (Round Rock, TX, USA). All solvents
(HPLC grade) were purchased from Thermo-Fisher
(Hanover Park, IL, USA). Anion exchange solid phase
extraction columns (Quaternary Amine with chloride
counter Ion, CUQAX12Z, 200 mg bed, 10 mL cartridge)
were purchased from United Chemical Technologies
(Bristol, PA, USA).
2.6. Quantification of Creatinine Concentration
of Specimens
Creatinine assays were quantified on an Olympus AU640
chemistry immunoanalyzer (Beckman Coulter, Inc., CA,
USA) using DRI® Creatinine-Detect reagent (Jaffe
method; Microgenics Corporation, Fremont, CA, USA)
2.7. Preparation of Calibration Standards and
Quality Control-PPFG
Stock solutions of PPFG and PPFG-d17 were prepared in
methanol at a concentration of 100 µg/mL. A PPFG
spiking standard working solution (0.40 µg/mL) was
prepared by further dilution with methanol. A PPFG-d17
internal standard working solution (0.40 µg/mL) was
prepared by dilution in methanol. A single-point cali-
brator (20 ng/mL) and a set of controls (0, 8, 25, and 80
ng/mL) were prepared by spiking 1 mL of certified
negative urine in a 13 × 100 glass culture tube with an
appropriate volume of PPFG spiking standard working
2.8. Specimen Preparation-PPFG
Each specimen was prepared separately by accurately
transferring 1 mL of urine to a 13 × 100 glass culture
tube. 50 µL of PPFG-d17 internal standard was added to
each specimen, calibrator or control and vortexed. The
tubes were centrifuged at 3400 × g for 5 minutes. The
samples were loaded onto the solid phase extraction
columns that had been preconditioned with 2 mL of
methanol, followed by 2 mL of deionized water. The
samples were allowed to flow through the columns at 1
mL/min. The columns were washed with 2 mL of
deionized water followed by 2 mL of methanol and then
dried under full vacuum for one minute. Drugs were
eluted from the columns into 13 × 100 glass tubes with 2
mL of methanolic formic acid (98:2) and evaporated
under nitrogen at 40˚C. The dried residues were recon-
stituted with 100 µL of deionized water by vortexing and
analyzed by LC-MS/MS.
2.9. LC-MS/MS Conditions-PPFG
Urine specimens were analyzed using an Agilent Techno-
logies 1200 system that consisted of a G1367D auto-
sampler, a G1379B degasser, G1312B binary pump, and
a G1310 isocratic pump (Wilmington, DE, USA). Sepa-
ration was achieved using a Phenomenex Synergi RP (50
mm × 2.0 mm, 2.0 µm particle size) column held at 50˚C
in a G1316B Thermostatted Column Compartment (Wil-
mington, DE, USA). Using a flow rate of 0.25 mL/min,
the solvent system was a gradient that consisted of A
(deionized water/0.1% formic acid) and B (acetonit-
rile/0.1% formic acid). The solvent program held B at
32% from 0.0 min to 8.0 min. The detector was an
Agilent Technologies 6460 tandem mass spectrometer
using electrospray ionization (ESI) in the negative mode
(Wilmington, DE, USA). The capillary voltage was set at
4000V, the nozzle voltage set at 1000V and the deso-
lvation gas (nitrogen) was heated to 350˚C with a flow of
10 l/min. The sheath gas (nitrogen) was heated to 300˚C
and delivered at 12 l/min. The internal standard (PPFG-
d17) was monitored using the m/z 370.2 > 193.9 (quanti-
fication ion; Frag = 155; CE = 20) and m/z 370.2 > 369.7
(qualifying ion; Frag = 155; CE = 0) transitions. The m/z
353.2 > 176.5 (quantification ion; Frag = 120; CE = 28),
the m/z 353.2 > 112.6 (quantification ion; Frag = 120; CE
= 12) and m/z 353.2 > 84.7 (qualifying ion; Frag = 120;
CE = 20) transitions were used to monitor PPFG where
Frag is the Fragmentation Voltage (V) and CE is the
Collision Energy (V). All data were processed using
MassHunter B.02.01 (Wilmington, DE, USA).
2.10. Identification Criteria-PPFG
The identification criteria used for this procedure in-
cluded four components: retention time, signal to noise,
baseline resolution and relative ion intensity. The
retention time of each analyte was required to be within
0.2 min of the calibrator. A signal to noise of greater than
3:1 was required of each ion chromatogram. A minimum
of 90% return to baseline was required to consider a peak
to be adequately resolved from a co-eluting peak. The
relative ion intensity of the productions for each analyte
(mass ratio) was required to be within 20% of the
corresponding relative ion intensity of the calibrator.
Copyright © 2013 SciRes. PP
Long-Term Detection of Propofol Glucuronide in Urine Following
Anesthetic Induction and Maintenance with Propofol
3. Results
Our limit of detection (LOD) in all three of these studies
was 4 ng/mL, and our limit of quantitation (LOQ) was 8
ng/mL. Creatinine secretion from muscles is relatively
constant in an individual, and PPFG concentrations were
normalized to 100 mg/dL creatinine levels to correct for
differences in urinary production and flow-rate by the
patient resulting from fluctuations in hydration levels
Urine samples in the oral ingestion pilot study (pilot
study #1) were collected when the subjects needed to
void, and as such occurred at irregular intervals (Table 1).
We were only able to collect samples from subject #2 for
three days, and that subject’s complete urinary PPFG
profile was not available as a result. Subjects #1, #3, and
#4 all exhibited urinary profiles well above LOD/LOQ
out to 5 - 6 days (120 - 154 hours) following the last oral
dose. The urinary PPFG profile data of these subjects
most nearly followed an exponential decay trend (Figure
1), however, this trend explains the behavior of the data
only moderately well (R2 = 0.681), likely due to the small
size of our sample population and the wide range in
physical variables of the subjects in the sample. None of
the volunteers reported any anesthetic or euphoric feel-
ings associated with ingesting propofol orally.
Of the de-identified nurse anesthetist samples from the
second pilot study, only two samples measured above the
LOD/LOQ (4.58 ng/mL and 17.34 ng/mL; normalized to
100 mg/dL creatinine; Table 2). The average of the
remaining 25 samples was 0.23 ng/mL over a range of
0.01 ng/mL to 2.20 ng/mL (normalized to 100 mg/dL
Thirteen urine specimens were collected periodically
from the colonoscopy patient over a period of 28 days
post-anesthesia (Table 3). The disappearance profile for
PPFG in this patient displayed an exponential decay trend
(R2 = 0.953; Figure 2). Surprisingly, PPFG was detec-
table at levels well above the LOD/LOQ for as long as 28
days post anesthesia.
4. Discussion
4.1. Disappearance Profile of Urinary Propofol
To our knowledge, only one other study has examined
the long-term profile of urinary PPFG (Bleeker et al.,
2008), which sampled blood and urine of patients out to
15 and 60 hours post-anesthesia respectively [8]. Based
on urinary clearance rates and percentage of recovered
PPFG, Bleeker et al. (2008) suggested that glucuroni-
dation of propofol would require 5 - 6 days to reach
completion and total clearance of propofol from the body,
however, the post-colonoscopy results presented here
Table 1. Urinary propofol glucuronide following sub-thera-
peutic dosing by oral ingestion: pilot study #1.1.
Post Dosing
PPFG2 (ng/mL)
#1/6 3222 15.7 20,522
#1/24 1237 50.7 2440
#1/36 183 31.2 587
#1/48 300 65.2 460
#1/72 109 102.5 106
#1/96 45 136.2 33
#1/120 30 115.0 26
#2/6 33,119 132.2 25,052
#2/24 5819 257.7 2258
#2/48 761 149.6 509
#2/72 493 193.7 255
#3/13.5 5573 57.1 9760
#3/20 451 74.9 602
#3/56.5 177 93.4 190
#3/81 326 142.5 229
#3/104 408 169.3 241
#3/129.5 358 243.3 147
#3/154 169 160.1 106
#4/22 9000 61.9 14,540
#4/37 853 68.0 1254
#4/49 226 42.7 529
#4/64.5 173 73.9 234
#4/86 103 79.2 130
#4/98 204 96.5 211
#4/99 215 111.1 194
#4/107.5 32 30.5 105
#4/118.5 91 87.9 104
#4/131.5 68 78.4 87
#4/143 89 88.4 101
#4/153 14 13.4 104
1Propofol glucuronide, creatinine and normalized propofol concentrations in
urine specimens collected from four individuals following 14 daily doses of
sub-therapeutic (50 mg), orally ingested propofol. Subjects consisted of two
males and two females between the ages of 45 - 65 years old and 150 - 300
lbs. 2Normalized PPFG concentrations are normalized to 100 mg/dL creat-
Copyright © 2013 SciRes. PP
Long-Term Detection of Propofol Glucuronide in Urine Following
Anesthetic Induction and Maintenance with Propofol
Table 2. Urinary propofol glucuronide resulting from inci-
dental exposure: pilot study #2.1.
Subject PPFG
PPFG2 (ng/mL)
#1 0.06 124.2 0.05
#2 0.03 136.3 0.02
#3 0.07 94.5 0.07
#4 0.05 159.3 0.03
#5 1.00 45.4 2.20
#6 0.01 28.6 0.04
#7 0.58 146.8 0.40
#8 0.02 68.5 0.03
#9 0.03 91.0 0.03
#10 0.01 50.6 0.02
#11 0.05 112.0 0.05
#12 0.01 188.9 0.01
#13 0.01 36.2 0.03
#14 0.32 213.6 0.15
#15 7.24 158.1 4.58
#16 0.02 65.9 0.03
#17 1.35 151.2 0.89
#18 11.2 64.6 17.34
#19 0.03 89.7 0.03
#20 0.44 126.6 0.35
#21 0.05 94.7 0.05
#22 0.01 48.6 0.02
#23 0.12 92.8 0.13
#24 0.65 194.0 0.34
#25 0.52 206.9 0.25
#26 0.50 178.2 0.28
#27 0.45 201.7 0.22
1Propofol glucuronide, creatinine and normalized propofol concentrations in
urine specimens collected from nurse anesthetists immediately following 8
hour shifts in surgical rooms during the use of propofol for patient
anesthesia. 2Normalized PPFG concentrations are normalized to 100 mg/dL
demonstrate easily measurable excretion of PPFG as far
out as 28 days (Table 3 and Figure 2).
The data from our oral ingestion pilot study #1 (Table
1) also showed clearly measurable levels of urinary
PPFG excretion as far as 6.4 days (154 hours) post-
dosing (Figure 1) in line with the results from Bleeker
Table 3. Propofol glucuronide, creatinine and normalized
propofol concentrations in urine specimens collected follo-
wing anesthetic induction and maintenanc e with propofol.
Subject PPFG
PPFG1 (ng/mL)
1 1656 16.9 9799
4 627 13.1 4786
9 1026 34.3 2991
10 268 10.0 2680
11 282 14.3 1972
12 200 19.4 1031
14 149 21.3 700
17 141 20.0 705
18 204 30.0 680
21 679 100.0 679
22 27 10.0 270
26 49 40.0 123
28 11 10.0 110
1Normalized PPFG concentrations are normalized to 100 mg/dL creatinine.
Figure 1. Disappearance profile of urinary propofol glu-
curonide following 14 daily sub-therapeutic (50 mg) doses
by oral ingestion: pilot study #1.
et al. (2008). The oral ingestion data is interesting, in that
even at sub-therapeutic doses (50 mg daily) delivered
through the highly acidic stomach compartment, appre-
ciable recovery of urinary PPFG was observed, perhaps
suggesting that deep tissue storage (i.e. fat reserves,
muscle tissues) of propofol occurs very quickly follo-
wing dosing, and lasts much longer than previous data
have suggested.
Copyright © 2013 SciRes. PP
Long-Term Detection of Propofol Glucuronide in Urine Following
Anesthetic Induction and Maintenance with Propofol
Figure 2. Disappearance profile of urinary propofol
glucuronide following intravenous induction and mainte-
nance of anesthesia.
Bleeker et al. (2008) hypothesized that renal reuptake,
presumably following release from sequestration in deep
tissues, and subsequent renal glucuronidation play a
major role in terminal elimination of propofol, and the
results presented here suggest their hypothesis is worth
closer pharmacokinetic investigation [8], though glucuro-
nidation may just as likely occur by the hepatic pathway
after rerelease. PPFG, like propofol, is highly lipophilic,
and the long-term excretion profile observed here may be
from slow release of both propofol and PPFG, with
subsequent conjugation of the parent compound. Further
study is necessary to completely elucidate the exact
nature and timing of storage and release.
4.2. Propofol vs. PPFG for the Detection of
Propofol Use and Abuse
Despite its narrow therapeutic window [7] propofol has a
high potential for abuse among healthcare professionals
with access to propofol stocks [18], and propofol abuse
has become a concern in the healthcare community [6].
The addictive nature of propofol has been previously
demonstrated [19,20], and several fatalities due to acute
intoxication without respiratory monitoring have occurr-
ed [10-14]. Data suggests that second-hand exposure to
propofol is high in hospital operating rooms and may
cause sensitization from chronic exposure, potentially
leading to an increased risk for use and abuse by anes-
thesia and surgical professionals [21,22]. More attention
to inventory control for propofol stocks may be war-
ranted [6], and screening to prevent non-procedural mis-
use and abuse by healthcare professionals with access
may be needed. Recent research has shown that the
course of propofol dependence can be rapid, and is often
accompanied by frequent physical injury of the user [23].
Although the population of propofol abusers is low, that
group carries the additional burden of a fatality rate (28%)
that is extremely high when compared with any tradi-
tional substance of abuse [6]. The importance of clear
identification of propofol abuse in at risk healthcare
professionals cannot be overstated.
The results shown here, along with those from Bleeker
et al. (2008), demonstrate that PPFG is a more reliable
biomarker for propofol abuse testing and monitoring than
propofol itself. Although propofol and PPFG have been
detected in several matrices including blood, urine, and
hair [24], as well as in fingernails by our laboratory group
(data not shown), a 28 day window of detection in urine,
as is shown here, would be more than sufficient as the
most cost-effective and efficient method of screening.
Patterns of addiction seen with propofol indicate abuse of
the compound involves multiple injections on frequent
occasions [10-14,20,23], and it is highly unlikely the
urinary PPFG profile for such behavior would show
faster terminal elimination from the body than is seen in
both the anesthetic and oral ingestion datasets presented
here (Figures 1 and 2).
Data from pilot study #2 involving nurse anesthetists
shows that passive exposure to aerosolized propofol in
the surgical environment provides a urinary PPFG profile
that is much different, and easily distinguishable, from
that of a person who has been administered the anesthetic
regardless of the route of administration. This suggests
that it should be easy to identify propofol abusers from
the general population of anesthesia professionals, and a
positive result cutoff of 200 ng/mL in urine specimens
should be sufficient to identify a person who is misusing
propofol for recreational purposes.
5. Conclusion
The results presented here demonstrate that PPFG has a
very long and robust disappearance profile in urine, and
has the potential to easily distinguish propofol abusers
from the greater population of healthcare professionals.
To our knowledge, this is the longest window of detec-
tion that has been demonstrated following propofol
ingestion of any sort. Propofol has a high potential for
abuse and is increasingly a cause for concern in the
healthcare community, and routine testing of healthcare
professionals with access to the compound may be
warranted. Lack of scheduling by the United States Drug
Enforcement Administration has resulted in easy and
under-regulated access to propofol in most hospitals
where no inventory control is present. Propofol itself has
a very short window of detection in blood and urine, and
the data presented here suggest that measuring PPFG in
urine samples is an efficient and reliable tool for routine
screening for propofol use and abuse.
Copyright © 2013 SciRes. PP
Long-Term Detection of Propofol Glucuronide in Urine Following
Anesthetic Induction and Maintenance with Propofol
Copyright © 2013 SciRes. PP
[1] C. M. Smith and A. M. Reynard, “Textbook of Pharma-
cology,” Harcourt Publishers Ltd., San Diego, 1992.
[2] A. Gupta, T. Stierer, R. Zuckerman, N. Sakima, S. D.
Parker and L. A. Fleisher, “Comparison of Recovery Pro-
file after Ambulatory Anesthesia with Propofol, Isoflu-
rane, Sevoflurane and Desflurane: A Systematic Review,”
Anesthesia & Analgesia, Vol. 98, No. 3, 2004, pp. 632-
[3] E. I. Eger, “Characteristics of Anesthetic Agents Used for
Induction and Maintenance of General Anesthesia,” Ame-
rican Journal of Health-System Pharmacy, Vol. 61, Suppl.
4, 2004, pp. S3-S10.
[4] B. Fulton and E. M. Sorkin, “Propofol. An Overview of
Its Pharmacology and a Review of Its Clinical Efficacy in
Intensive Care Sedation,” Drugs, Vol. 50, No. 4, 1995, pp.
[5] J. Kanto and E. Gepts, “Pharmacokinetic Implications of
the Clinical Use of Propofol,” Clinical Pharmacokinetics,
Vol. 17, No. 5, 1989, pp. 308-326.
[6] P. E. Wischmeyer, B. R. Johnson, J. E. Wilson, C. Ding-
mann, H. M. Bachman, E. Roller, Z. V. Tran and T. K.
Henthorn, “A Survey of Propofol Abuse in Academic
Anesthesia Programs,” Anesthesia & Analgesia, Vol. 105,
No. 4, 2007, pp. 1066-1071.
[7] C. F. Ward, “Propofol: Dancing with the ‘White Rabbit’,”
Bulletin of the California Society of Anesthesiology, Vol.
57, No. 2, 2008, pp. 61-63.
[8] C. Bleeker, T. Vree, A. Lagerwerf, and E. Williams-van
Bree, “Recovery and Long-Term Renal Excretion of Pro-
pofol, Its Glucuronide, and Two Di-Isopropylquinol Glu-
curonides after Propofol Infusion during Surgery,” British
Journal of Anaesthesia, Vol. 101, No. 2, 2008, pp. 207-
[9] P. Favetta, C. S. Degoute, J. P. Perdrix, C. Dufresne, R.
Boulieu and J. Guitton, “Propofol Metabolites in Man
Following Propofol Induction and Maintenance,” British
Journal of Anaesthesia, Vol. 88, No. 5, 2008, pp. 653-658.
[10] O. H. Drummer, “A Fatality Due to Propofol Poisoning,”
Journal of Forensic Science, Vol. 37, No. 4, 1992, pp.
[11] T. C. Chao, D. S. Lo, P. P. Chui and T. H. Koh, “The First
Fatal 2, 6-Di-Isopropylphenol (Propofol) Poisoning in
Singapore: A Case Report,” Forensic Science Interna-
tional, Vol. 66, No. 1, 1994, pp. 1-7.
[12] S. Iwersen-Bergmann, P. Rosner, H. C. Kuhnau, M. Junge
and A. Schmoldt, “Death after Excessive Propofol Abuse,”
International Journal of Legal Medicine, Vol. 114, No.
4-5, 2001, pp. 248-251.
[13] E. F. Kranioti, A. Mavroforou, P. Mylonakis and M. Mi-
chalodimitrakis, “Lethal Self Administration of Propofol
(Diprivan). A Case Report and Review of the Literature,”
Forensic Science International, Vol. 167, No. 1, 2007, pp.
[14] G. Klausz, K. Rona, I. Kristof and K. Toro, “Evaluation
of a Fatal Propofol Intoxication Due to Self Administra-
tion,” Journal of Forensic and Legal Medicine, Vol. 16,
No. 5, 2009, pp. 287-289.
[15] H. M. Bryson, B. R. Fulton and D. Faulds, “Propofol. An
Update of Its Use in Anesthesia and Conscious Sedation,”
Drugs, Vol. 50, No. 3, 1995, pp. 513-559.
[16] W. R. Needleman, M. Porvaznik and D. Ander, “Cre-
atinine Analysis in Single Collection Urine Specimens,”
Journal of Forensic Sciences, Vol. 37, No. 4, 1992, pp.
[17] “DRI® Creatinine-Detect Test,” Product Insert, Micro-
genics Corporation, Fremont, 2005.
[18] O. Grundmann, “Propofol: An Analytical and Medico-
Legal Challenge,” Forensic Magazine, Vol. 7, No. 5,
2010, pp. 13-15.
[19] J. P. Zacny, J. L. Lichtor, W. Thompson and J. L. Apfel-
baum, “Propofol at a Subanesthetic Dose May Have
Abuse Potential in Healthy Volunteers,” Anesthesia and
Analgesia, Vol. 77, No. 3, 1993, pp. 544-552.
[20] U. Bonnet, J. Harkener and N. Scherbaum, “A Case Re-
port of Propofol Dependence in a Physician,” Journal of
Psychoactive Drugs, Vol. 40, No. 2, 2008, pp. 215-217.
[21] P. F. McAuliffe, M. S. Gold, L. Baipai, M. L. Merves, K.
Frost-Pineda, R. M. Pomm, B. A. Goldberger, R. J.
Melker and J. C. Cendan, “Second-Hand Exposure to
Aerosolized Intravenous Anesthetics Propofol and Fen-
tanyl May Cause Sensitization and Subsequent Opiate
Addiction among Anesthesiologists and Surgeons,” Medi-
cal Hypotheses, Vol. 66, No. 5, 2006, pp. 874-882.
[22] L. J. Merlo, B. A. Goldberger, D. Kolodner, K. Fitzgerald
and M. S. Gold, “Fentanyl and Propofol Exposure in the
Operating Room: Sensitization Hypotheses and Further
Data,” Journal of Addictive Disorders, Vol. 27, No. 3,
2008, pp. 67-76.
[23] P. H. Earley and T. Finver, “Addiction to Propofol: A
Study of 22 Treatment Cases,” Journal of Addiction
Medicine, Vol. 7, No. 3, 2013, pp. 169-176.
[24] V. Cirimele, P. Kintz, S. Doray and B. Ludes, “Determi-
nation of Chronic Abuse of the Anesthetic Agents Mida-
zolam and Propofol as Demonstrated by Hair Analysis,”
International Journal of Legal Medicine, Vol. 116, No. 1,
2002, pp. 54-57.