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Summary

One pentobarbital powder sample and a syringe containing a solution with suspended
solids provided by Georgia Department of Corrections were analyzed by x-ray powder
diffraction (XRPD), differential scanning calorimetry (DSC), and infrared (IR)
spectroscopy. Information for the samples provided is listed in Table 1.
Table 1. API Samples Provided
Triclinic Sample
Number

Sample Description

Pentobarbital Sodium, CAS# 57-33-0,


Purity 99.00%, Case # - II-2015-1214
Pentobarbital Sodium, 50mg/mL,
Exp. 03/24/2015, Case # - II-2015-1214

TCL2758
TCL2759

Results
The filenames for the data collected from the powder sample and the solids from the
syringe are summarized in Table 2. The powder sample was able to be analyzed as
received. The solids from the syringe were isolated by centrifuging the material,
decanting the liquid, and allowing the material to air dry.
Table 2. Analytical Testing Filenames
Triclinic Sample
Number
TCL2758
TCL2759

XRPD Filename
RX1-7453
RX1-7454

XRPD
Page No.
6
6

DSC
Filename
DSC2.0911
DSC2.0912

DSC Page
No.
9
10

IR
Filename
IR782
IR783

IR Page
No.
11
11

An overlay of the XRPD patterns for the powder sample and the solids from the syringe
is displayed in Figure 1. The pattern for the powder sample provided shows a number
of broad discrete diffraction peaks overlaid on a raised baseline, suggesting that this
sample contains crystalline and non-crystalline material. The pattern for the solids
isolated from the syringe showed a number of broad, discrete, diffraction peaks
superimposed on a flat baseline, indicating that this sample is crystalline. Visual
comparison of the patterns showed that there were some similar peaks between the
patterns, but a number of unique peaks were also observed in the patterns.
In order to determine the identity of the materials in the samples, a database
search/match analysis was performed. Figure 2 shows an overlay of the XRPD pattern
for the powder sample with the database stick patterns for one solid form of
pentobarbital sodium, one solid form of pentobarbital, and sodium chloride [1]. These
three stick patterns describe all but two broad, low-intensity, high-angle reflections
observed in the XRPD pattern for the powder sample. This would suggest that these
three components comprise the majority of the sample. Figure 3 shows an overlay of
the XRPD pattern for the solids isolated from the syringe and the database stick
patterns for two different solid forms of pentobarbital [2]. These two stick patterns
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describe all but four low-intensity high-angle reflections observed in the pattern for the
solids isolated from the syringe. This would suggest that these two components
comprise the majority of this sample.
The results from the database search for the two patterns would suggest that the two
samples contain one common form of pentobarbital, but that the other components
comprising these samples are different. The powder sample appears to contain
pentobarbital sodium as its other major component, while the solids isolated from the
syringe contain another polymorph of pentobarbital as the other major component. This
would indicate that the sodium salt of pentobarbital broke apart when preparing the
solution in the syringe and polymorphs of the free base ultimately precipitated from the
solution in this sample.
The powder sample and the solids isolated from the syringe were also analyzed by DSC
and the thermograms are presented in Figures 4 and 5, respectively. The DSC results
are summarized in Table 3.
Table 3. DSC Results
Triclinic Sample
DSC
a
DSC Results
Number
Filename
TCL2758
DSC2.0911 Endos. at ~143 C (b), 220 C (b), 305 C (s), and 316 C (s)
TCL2759
DSC2.0912
Endos. at ~76 C (b), 140 C (b), and 246 C (b)
a. Endos. = endotherms; b = broad; s = sharp.

The thermograms for the two samples are quite different, with the only similarity being
that there is an event between 140 and 145 C for both samples. This would suggest
that the compositions of the two samples are largely different, but that there may be a
common component. This is consistent with the XRPD findings which suggested that
there was a common component between the samples, but other components were
different.
An overlay of the IR spectra for the two samples is presented in Figure 5. As with the
XRPD and DSC data, there are similarities between the spectra for the two samples. A
number of common bands are observed between the two spectra, but there are also
regions that show significant differences. A library search was performed for the
powder sample and a solid match was found to a library spectrum of pentobarbital
sodium [3]. The spectrum for the solids isolated from the syringe contained a number of
additional bands that were not observed in the library spectrum of the pentobarbital
sodium. No suitable matches were found that described these additional spectral
bands.

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Conclusions
Based on the analyses performed in this study, the powder sample is believed to
contain pentobarbital sodium, a polymorph of pentobarbital free base, and sodium
chloride. The solids isolated from the syringe are believed to contain two different
polymorphs of pentobarbital free base.

Experimental
XRPD
The Rigaku Smart-Lab X-ray diffraction system was configured for reflection BraggBrentano geometry using a line source X-ray beam. The x-ray source is a Cu Long
Fine Focus tube that was operated at 40 kV and 44 mA. That source provides an
incident beam profile at the sample that changes from a narrow line at high angles to a
broad rectangle at low angles. Beam conditioning slits are used on the line X-ray
source to ensure that the maximum beam size is less than 10 mm both along the line
and normal to the line. The Bragg-Brentano geometry is a para-focusing geometry
controlled by passive divergence and receiving slits with the sample itself acting as the
focusing component for the optics. The inherent resolution of Bragg-Brentano geometry
is governed in part by the diffractometer radius and the width of the receiving slit used.
Typically, the Rigaku Smart-Lab is operated to give peak widths of 0.1 2 or less. The
axial divergence of the X-ray beam is controlled by 5.0-degree Soller slits in both the
incident and diffracted beam paths.
The powder samples were prepared in a low background Si holder using light manual
pressure to keep the sample surfaces flat and level with the reference surface of the
sample holder. The single crystal Si low background holder has a small circular recess
(7 mm diameter and about 1 mm depth) that holds between 15 and 25 mg of powdered
material. Each sample was analyzed from 2 to 40 2 using a continuous scan of 6 2
per minute with an effective step size of 0.02 2.
DSC
DSC analyses were performed using a TA Instruments Q2000 differential scanning
calorimeter equipped with a refrigerated cooling system (RCS). Approximately 3 to 4
mg of each sample was weighted into an aluminum Tzero pan, covered with and
aluminum Tzero lid, and crimped. The sample cell was heated from ambient to 350 C
at a rate of 10 C/minute. An empty reference pan prepared in the same way was also
present in the cell to account for the heat flow properties of the pan. The DSC
instrument is controlled using the Thermal Advantage Release 5.2.5.
Infrared Spectroscopy IR
The IR spectra were acquired utilizing a Thermo Nicolet model 6700 Fourier-transform
(FT)-IR spectrophotometer equipped with a deuterated triglycine sulfate (DTGS)
detector, a potassium bromide (KBr) beamsplitter, and an electronically temperature
controlled (ETC) Ever-Glo IR source. The spectra were acquired using a SMART iTR
diamond attenuated total reflectance (ATR) sampling accessory with a spectral range of

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4000-525 cm-1. Each spectrum is the result of 128 co-added scans acquired at 2 cm-1
resolution. A single beam background scan of the air was acquired before the sample
scan allowing presentation of the spectrum in Log 1/R units. A wavelength calibration
was performed using polystyrene. (The Omnic 8.2 software package (Thermo-Nicolet)
was used to acquire, process, and evaluate the spectral data.)

References
1. International Centre for Diffraction Data PDF-4 2015 Organics Database,
downloaded and interfaced with Rigaku PDXL software at Triclinic Labs, card
numbers 00-029-1920 and 00-027-1597.
2. International Centre for Diffraction Data PDF-4 2015 Organics Database,
downloaded and interfaced with Rigaku PDXL software at Triclinic Labs, card
numbers 00-028-1648.
3. Sigma Biological Sample Library, Sample Index #9, Copyright 2008 Thermo
Fisher Scientific Inc.

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Figure 1. Overlay of XRPD patterns for the pentobarbital powder sample and the solids isolated from the syringe.

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Intensity (cps)

Analysis date
Sample name
File name

Comment

Qualitative analysis results

Phase name
Formula
sodium 5-ethyl-5-(1C11 H17 N2 Na O3
methylbutyl)
5-ethyl-5-(1C11 H18 N2 O3
barbiturate
methylbutyl)-1,3NaCl
Cl Na
diazinane-2,4,6trione, 5-ethyl-5-(1Phase
data pattern
methylbutyl)barbituric
acid

8.0e+003

6.0e+003

4.0e+003

2.0e+003

R201583.01

Qualitative Analysis Results

General information
2015/04/02 11:57:22

RX1-7453_Theta_2Theta.TXT

10

5-ethyl-5-(1-methylbutyl)-1,3-diazinane-2,4,6-trione,
acid, C11 H18 N2 O3, , 7.0500, 12.5455
sodium
5-ethyl-5-(1-methylbutyl) barbiturate, C11 H17 N2 5-ethyl-5-(1-methylbutyl)barbituric
Na O3, , 6.9900, 12.6537
sodium 5-ethyl-5-(1-methylbutyl) barbiturate, C11 H17 N2 Na O3, , 6.6500, 13.3035
sodium
5-ethyl-5-(1-methylbutyl) barbiturate, C11 H17 N25-ethyl-5-(1-methylbutyl)barbituric
Na O3, , 6.3500, 13.9350
5-ethyl-5-(1-methylbutyl)-1,3-diazinane-2,4,6-trione,
acid, C11 H18 N2 O3, , 6.2100, 14.2508
5-ethyl-5-(1-methylbutyl)-1,3-diazinane-2,4,6-trione,
5-ethyl-5-(1-methylbutyl)barbituric
acid, C11 H18 N2 O3, , 6.0100, 14.7276
sodium 5-ethyl-5-(1-methylbutyl) barbiturate,
C11 H17 N2 Na O3, , 5.9800, 14.8019

sodium 5-ethyl-5-(1-methylbutyl) barbiturate, C11 H17 N2 Na O3, , 14.1000, 6.2634


sodium 5-ethyl-5-(1-methylbutyl) barbiturate, C11 H17 N2 Na O3, , 12.0000, 7.3609
sodium 5-ethyl-5-(1-methylbutyl) barbiturate, C11 H17 N2 Na O3, , 11.1000, 7.9586
sodium 5-ethyl-5-(1-methylbutyl) barbiturate, C11 H17 N2 Na O3, , 9.9900, 8.8446
sodium 5-ethyl-5-(1-methylbutyl) barbiturate, C11 H17 N2 Na O3, , 8.9800, 9.8417
sodium 5-ethyl-5-(1-methylbutyl) barbiturate, C11 H17 N2 Na O3, , 8.5300, 10.3622
sodium 5-ethyl-5-(1-methylbutyl) barbiturate, C11 H17 N2 Na O3, , 7.8500, 11.2626

Figure 2. Overlay of the XRPD pattern for the powder sample with the database
patterns for pentobartbital sodium.

Figure of merit
1.161
1.833
2.282

5-ethyl-5-(1-methylbutyl)-1,3-diazinane-2,4,6-trione, 5-ethyl-5-(1-methylbutyl)barbituric acid, C11 H18 N2 O3, , 4.0000, 22.2061


sodium 5-ethyl-5-(1-methylbutyl) barbiturate, C11 H17 N2 Na O3, , 3.8600, 23.0223

sodium 5-ethyl-5-(1-methylbutyl) barbiturate, C11 H17


N2 Na O3, , 4.6700, 18.9882
5-ethyl-5-(1-methylbutyl)-1,3-diazinane-2,4,6-trione,
5-ethyl-5-(1-methylbutyl)barbituric
acid, C11 H18 N2 O3, , 4.6200, 19.1956
sodium 5-ethyl-5-(1-methylbutyl) barbiturate, C11 H17 N2 Na O3, , 4.4400, 19.9816
5-ethyl-5-(1-methylbutyl)-1,3-diazinane-2,4,6-trione, 5-ethyl-5-(1-methylbutyl)barbituric acid, C11 H18 N2 O3, , 4.3000, 20.6392

5-ethyl-5-(1-methylbutyl)-1,3-diazinane-2,4,6-trione, 5-ethyl-5-(1-methylbutyl)barbituric acid, C11 H18 N2 O3, , 5.1200, 17.3058


sodium 5-ethyl-5-(1-methylbutyl) barbiturate, C11 5-ethyl-5-(1-methylbutyl)barbituric
H17 N2 Na O3, , 4.9800, 17.7962
5-ethyl-5-(1-methylbutyl)-1,3-diazinane-2,4,6-trione,
acid, C11 H18 N2 O3, , 4.9400, 17.9415

sodium 5-ethyl-5-(1-methylbutyl) barbiturate, C11 H17 N2 Na O3, , 5.5500, 15.9559

Measurement date
Operator

20

Phase reg. detail


ICDD (PDF-4
Organics
2015 RDB)
ICDD (PDF-4
Organics
2015 RDB)
User
(COD3)

sodium 5-ethyl-5-(1-methylbutyl) barbiturate, C11 H17 N2 Na O3, , 3.5600, 24.9925


5-ethyl-5-(1-methylbutyl)-1,3-diazinane-2,4,6-trione, 5-ethyl-5-(1-methylbutyl)barbituric acid, C11 H18 N2 O3, , 3.4800, 25.5766
sodium
5-ethyl-5-(1-methylbutyl) barbiturate, C11 H175-ethyl-5-(1-methylbutyl)barbituric
N2 Na O3, , 3.3600, 26.5064
5-ethyl-5-(1-methylbutyl)-1,3-diazinane-2,4,6-trione,
acid, C11 H18 N2 O3, , 3.3200, 26.8317
NaCl, Cl Na, (1 1 1), 3.2620, 27.3179
5-ethyl-5-(1-methylbutyl)-1,3-diazinane-2,4,6-trione, 5-ethyl-5-(1-methylbutyl)barbituric acid, C11 H18 N2 O3, , 3.1400, 28.4012
5-ethyl-5-(1-methylbutyl)-1,3-diazinane-2,4,6-trione, 5-ethyl-5-(1-methylbutyl)barbituric acid, C11 H18 N2 O3, , 3.0900, 28.8706
5-ethyl-5-(1-methylbutyl)-1,3-diazinane-2,4,6-trione, 5-ethyl-5-(1-methylbutyl)barbituric acid, C11 H18 N2 O3, , 3.0100, 29.6553
5-ethyl-5-(1-methylbutyl)-1,3-diazinane-2,4,6-trione, 5-ethyl-5-(1-methylbutyl)barbituric acid, C11 H18 N2 O3, , 2.9200, 30.5913
5-ethyl-5-(1-methylbutyl)-1,3-diazinane-2,4,6-trione,
5-ethyl-5-(1-methylbutyl)barbituric acid, C11 H18 N2 O3, , 2.8560, 31.2942
NaCl, Cl Na, (2 0 0), 2.8250, 31.6468
5-ethyl-5-(1-methylbutyl)-1,3-diazinane-2,4,6-trione, 5-ethyl-5-(1-methylbutyl)barbituric acid, C11 H18 N2 O3, , 2.6200, 34.1959

2015/03/27 09:46:36

DB card number
00-029-1920
00-027-1597
150357

sodium 5-ethyl-5-(1-methylbutyl) barbiturate, C11 H17 N2 Na O3, 00-029-1920


5-ethyl-5-(1-methylbutyl)-1,3-diazinane-2,4,6-trione, 5-ethyl-5-(1-methylbutyl)barbituric acid, C11 H18 N2 O3, 00-027-1597
NaCl, Cl Na, 150357

0.0e+000

30

40

2-theta (deg)

Page 7 of 13

Phase name
Formula
5-ethyl-5-(1C11 H18 N2 O3
methylbutyl)-1,35-ethyl-5-(1C11 H18 N2 O3
diazinane-2,4,6methylbutyl)barbituric
trione, 5-ethyl-5-(1acid
Phase
data pattern
methylbutyl)barbituric
acid
1.5e+004

1.0e+004

5.0e+003

R201583.01

Qualitative Analysis Results

General information

Analysis date
Sample name
File name
2015/04/02 12:14:47

RX1-7454_Theta_2Theta.TXT

Comment

Qualitative analysis results

10

5-ethyl-5-(1-methylbutyl)-1,3-diazinane-2,4,6-trione,
5-ethyl-5-(1-methylbutyl)barbituric
acid,H18
C11N2
H18
O3,5-ethyl-5-(1-methylbutyl)barbituric
, 6.2100,
14.2508
acid, C11 H18 N2 O3, , 6.2100, 14.2508
5-ethyl-5-(1-methylbutyl)barbituric
acid, C11
O3,N2, 6.0700,
14.5812
5-ethyl-5-(1-methylbutyl)-1,3-diazinane-2,4,6-trione,
5-ethyl-5-(1-methylbutyl)barbituric
acid, C11 H18 N2 O3, , 6.0100, 14.7276

5-ethyl-5-(1-methylbutyl)-1,3-diazinane-2,4,6-trione, 5-ethyl-5-(1-methylbutyl)barbituric acid, C11 H18 N2 O3, , 7.0500, 12.5455

5-ethyl-5-(1-methylbutyl)barbituric acid, C11 H18 N2 O3, , 13.8000, 6.3997

Intensity (cps)

Figure 3. Overlay of the XRPD pattern for the solids isolated from the syringe with the
database patterns for two polymorphs of pentobarbital.

Figure of merit
1.253
1.468

5-ethyl-5-(1-methylbutyl)-1,3-diazinane-2,4,6-trione,
5-ethyl-5-(1-methylbutyl)barbituric
acid, C11 H18 N2 O3, , 5.1200, 17.3058
5-ethyl-5-(1-methylbutyl)barbituric
acid, C11 H18 N2 O3,
, 5.0700, 17.4778
5-ethyl-5-(1-methylbutyl)-1,3-diazinane-2,4,6-trione,
5-ethyl-5-(1-methylbutyl)barbituric
acid, C11 H18 N2 O3, , 4.9400, 17.9415
5-ethyl-5-(1-methylbutyl)barbituric
acid, C11 H18 N2 O3, , 4.9200,
18.0151
5-ethyl-5-(1-methylbutyl)barbituric acid, C11 H18 N2 O3,
, 4.6600, 19.0293
5-ethyl-5-(1-methylbutyl)-1,3-diazinane-2,4,6-trione,
5-ethyl-5-(1-methylbutyl)barbituric
acid, C11 H18 N2 O3, , 4.6200, 19.1956

5-ethyl-5-(1-methylbutyl)barbituric acid, C11 H18 N2 O3, , 3.7400, 23.7716

5-ethyl-5-(1-methylbutyl)-1,3-diazinane-2,4,6-trione,
5-ethyl-5-(1-methylbutyl)barbituric
acid, C11 H18 N2 O3, , 4.0000, 22.2061
5-ethyl-5-(1-methylbutyl)barbituric
acid, C11 H18 N2 O3,
, 3.9500, 22.4908

5-ethyl-5-(1-methylbutyl)-1,3-diazinane-2,4,6-trione,
5-ethyl-5-(1-methylbutyl)barbituric
acid, C11 H18 N2 O3, , 4.3000, 20.6392
5-ethyl-5-(1-methylbutyl)barbituric
acid, C11 H18 N2 O3,
, 4.2900, 20.6878

Measurement date
Operator

20

Phase reg. detail


ICDD (PDF-4
Organics
2015 RDB)
ICDD (PDF-4
Organics 2015 RDB)

5-ethyl-5-(1-methylbutyl)-1,3-diazinane-2,4,6-trione, 5-ethyl-5-(1-methylbutyl)barbituric acid, C11 H18 N2 O3, , 3.1400, 28.4012


5-ethyl-5-(1-methylbutyl)-1,3-diazinane-2,4,6-trione, 5-ethyl-5-(1-methylbutyl)barbituric acid, C11 H18 N2 O3, , 3.0900, 28.8706
5-ethyl-5-(1-methylbutyl)-1,3-diazinane-2,4,6-trione, 5-ethyl-5-(1-methylbutyl)barbituric acid, C11 H18 N2 O3, , 3.0100, 29.6553
5-ethyl-5-(1-methylbutyl)barbituric
acid, C11 H18 N2 O3,
, 2.9400, 30.3782
5-ethyl-5-(1-methylbutyl)-1,3-diazinane-2,4,6-trione,
5-ethyl-5-(1-methylbutyl)barbituric
acid, C11 H18 N2 O3, , 2.9200, 30.5913
5-ethyl-5-(1-methylbutyl)barbituric
acid, C11 H18 N2 O3,
, 2.8650, 31.1934
5-ethyl-5-(1-methylbutyl)-1,3-diazinane-2,4,6-trione,
5-ethyl-5-(1-methylbutyl)barbituric
acid, C11 H18 N2 O3, , 2.8560, 31.2942

5-ethyl-5-(1-methylbutyl)-1,3-diazinane-2,4,6-trione,
acid, C11 H18 N2 O3, , 3.3200, 26.8317
5-ethyl-5-(1-methylbutyl)barbituric
acid, C11 H18 N2 O3,5-ethyl-5-(1-methylbutyl)barbituric
, 3.2800, 27.1651

5-ethyl-5-(1-methylbutyl)-1,3-diazinane-2,4,6-trione, 5-ethyl-5-(1-methylbutyl)barbituric acid, C11 H18 N2 O3, , 3.4800, 25.5766

5-ethyl-5-(1-methylbutyl)barbituric
acid, C11
C11 H18
H18 N2
N2 O3,
O3,
2.6350, 34.1959
33.9953
5-ethyl-5-(1-methylbutyl)-1,3-diazinane-2,4,6-trione,
5-ethyl-5-(1-methylbutyl)barbituric
acid,
5-ethyl-5-(1-methylbutyl)barbituric
,, 2.6200,
acid, C11 H18 N2 O3, , 2.6200, 34.1959

2015/03/27 09:46:36

DB card number
00-027-1597
00-028-1648

5-ethyl-5-(1-methylbutyl)-1,3-diazinane-2,4,6-trione, 5-ethyl-5-(1-methylbutyl)barbituric acid, C11 H18 N2 O3, 00-027-1597


5-ethyl-5-(1-methylbutyl)barbituric acid, C11 H18 N2 O3, 00-028-1648

0.0e+000

30

40

2-theta (deg)

Page 8 of 13

Figure 4. DSC thermogram for pentobarbital powder sample.


Sample: TCL2757
Size: 2.4250 mg
Method: Ramp

File: T:...\2015051\Data\DSC\DSC2.0911
Operator: TLC
Run Date: 26-Mar-2015 15:58
Instrument: DSC Q2000 V24.11 Build 124

DSC

143.16C

219.70C

-1

Heat Flow (W/g)

305.09C

-2
316.18C

-3

-4
0

50

100

150

200

Temperature (C)

Exo Up

R201583.01

250

300

350
Universal V4.5A TA Instruments

Page 9 of 13

Figure 5. DSC thermogram for solids isolated from the syringe.

Sample: 304-32-2
Size: 5.6540 mg
Method: Ramp

File: T:...\2015051\Data\DSC\DSC2.0912
Operator: TLC
Run Date: 26-Mar-2015 16:38
Instrument: DSC Q2000 V24.11 Build 124

DSC

0.5

Heat Flow (W/g)

0.0

-0.5

76.13C
245.95C

-1.0

-1.5

139.58C

-2.0
0

50

100

150

200

Temperature (C)

Exo Up

R201583.01

250

300

350
Universal V4.5A TA Instruments

Page 10 of 13

Figure 6. Overlay of the IR spectra for pentobarbital powder sample and the solids isolated from the syringe.

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Figure 7. Overlay of the IR spectrum of the pentobarbital powder sample and a library spectrum for pentobarbital sodium.

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Figure 8. Overlay of the IR spectrum of the pentobarbital powder sample, the solids isolated from the syringe, and a
library spectrum for pentobarbital sodium.
0.50 TCL2757; Pentobarbital

Log

0.40

Signature: Unable to v erif y digital signature. The data has been changed.

0.30
0.20
0.10
0.00
0.8

#304-32-2; Pentobarbit al (f rom TCL2758)


Signature: Unable to v erif y digital signature. The data has been changed.

Log

0.6
0.4
0.2

1.0 PENTOBARBITAL SODIUM--DEA SCHEDUL

Abs

0.8 Signature: Not signed


0.6
0.4
0.2

3500

3000

2500

2000

1500

Wav enumbers (cm-1)

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1000