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AN-RS-038
Detection of LSD on Blotter Paper
Raman, SERS, and Drug Enforcement
Summary
Lysergic acid diethylamine (LSD), or «acid» as it is popularly known, is a Schedule 1 controlled
substance responsible for potent euphoria-inducing and sensory-altering properties. Long
lasting psychopathological consequences, such as auditory/visual hallucinations and
psychoses, have been documented in vulnerable LSD users. LSD is typically spotted on
colorful, absorbent «blotter» papers for sublingual and oral administration. Convenient
detection of LSD requires a flexible system capable of trace detection of the target compound
in the presence of potential interferents—including dyes, substrates, and solvents—with
minimal sample processing. This Application Note describes real-world test simulations using
SERS (Surface-Enhanced Raman Scattering) materials and test samples consisting of ink-
printed and color dyed paper matrices spiked with LSD. Simple extraction procedures are
highlighted to lift the target compound and remove fillers, inks and dyes that fluoresce or
otherwise confound identification of LSD.
MISA (Metrohm Instant SERS Analyzer) and MIRA XTR DS (Metrohm Instant Raman
Analyzer) are ideal solutions for rapid field identification of a range of illicit and dangerous
chemical substances. Easy-to-use test kits and flexible sampling allow rapid and accurate
interrogation of suspect materials with minimal time, training, and expense.
Introduction
Raman spectroscopy is a superior method for detection of bulk materials and chemicals,
although it lacks sensitivity for trace detection. When LSD-saturated paper products are
interrogated with Raman, the spectrum is dominated by the substrate signal. SERS, however,
is sensitive enough to detect the active ingredient in typical single-dose street samples
containing 20–400 g of LSD.
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Configuration
2.950.0020 - MISA Advanced
Metrohm Instant SERS Analyzer (MISA) is a high performance, portable
analyzer system used for rapid, trace level detection / identification of
illicit materials, food additives and food contaminants. MISA features a
high-efficiency spectrograph equipped with Metrohm's unique Orbital-
Raster-Scan (ORS) technology. It has a minimal footprint and extended
battery life, perfect for on-site testing or mobile laboratory applications.
MISA offers various Laser Class 1 attachments for flexible sampling
options. Analyzer operation is available through BlueTooth or USB
connectivity.The MISA Advanced package is a complete package that
allows the user to perform SERS analyses using Metrohm's nanoparticle
solutions and P-SERS strips.The MISA Advanced package includes a
MISA Vial Attachment, a P-SERS Attachment, a ASTM Calibration
Standard, a USB Mini Cable, a USB Power Supply and MISA Cal
software for operating the MISA instrument. A ruggedized protective
case is also provided to securely store the instrument and accessories.
2.926.0110 - MIRA XTR DS Basic
MIRA XTR DS is an alternative for high power 1064 nm systems.
Powered by advanced computational processing, MIRA XTR DS uses a
more sensitive 785 nm laser light along with XTR algorithms to eXTRact
the Raman data from the sample fluorescence. MIRA XTR DS also
features Orbital Raster Scanning (ORS) to provide better coverage of
the sample increasing the accuracy of the results.The Basic package is
a starter package that contains the basic components required for
operating the MIRA XTR DS. The Basic package includes Calibration
Standard, Intelligent Universal Attachment, and the library of Illicit
Materials. Class 3B operation.
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2.926.0120 - MIRA XTR DS Advanced
MIRA XTR DS is an alternative for high power 1064 nm systems.
Powered by advanced AI and Machine Learning, MIRA XTR DS uses a
more sensitive 785 nm laser along with XTR algorithms to eXTRact the
Raman data from the sample fluorescence. MIRA XTR DS also features
Orbital Raster Scanning (ORS) to provide better coverage of the sample
increasing the accuracy of the results.The Advanced package includes
MIRA Lib KnowItAllTM Full Raman Library Collection of over 19,500
samples, MIRA XTR DS Raman spectral library for Illicit Materials,
Calibration Standard, Intelligent Universal Attachment, Right-angle
Attachment, Vial Attachment, and MIRA SERS Attachment. A complete
package for any type of analysis. Class 3B operation.
607506450 - ID Kit - Ag NP
The ID Kit - Ag NP contains the components a Mira / Misa user requires
to perform a SERS analysis using silver colloidal solution. The kit
contains a disposable spatula, dropper, sample vials, and a bottle of
silver colloid.
LSD on chromatography paper
SERS measurements of LSD samples extracted from unprinted chromatography paper were
collected. Serial dilutions of 1 mg/mL LSD in methanol were pipetted onto individual squares of
paper, yielding test LSD concentrations of 20, 10, 5, 2, and 1 g/0.635 cm . Once dry, each
2
square was placed in a glass vial, shaken with 500 L of Ag colloid and rested for five minutes to
facilitate extraction. The paper was removed, and 100 L of 0.9% NaCl was added to the vial.
This mixture was gently shaken and allowed to rest for one minute before the vial was inserted
into the vial holder attachment on MISA and measured using the ID Kit OP.
Figure 1 shows the concentration profile of LSD on chromatography paper, indicating efficient
and rapid aqueous extraction of the target compound. Of note is the absence of spectral
interference from the paper substrate. Inspection of the concentration profile suggests a LOD
(limit of detection) of approximately 1 g LSD, which is sufficiently sensitive for confident
screening of confiscated drug samples.
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Figure 1. Reference LSD on chromatography paper concentration profile.
LSD on colored printer paper
To evaluate the effects of colorants on SERS identification of LSD extracted from paper, the
procedure outlined in the previous section was replicated with both paper laser-printed with
colored toner and paper coated with a mixture of food dyes. As the bottom two spectra in
show, both treatments significantly reduce the intensity and resolution of the LSD
Figure 2
signal. This is largely due to the fluorescence emissions of colorants, which serve to lower the
signal-to-noise (S/N) ratio of signature peaks.
A simple sample clean-up procedure based on liquid-liquid extraction improved signal intensity
dramatically. In this modification of the extraction procedure, dried LSD-saturated paper was
added to a glass vial containing 500 L of water and 10 L of 1 mol/L NaOH. This mixture was
shaken gently, 500 L of dichloromethane (DCM) was added, and the subsequent mixture was
shaken again. After phase separation, the (bottom) DCM layer containing LSD was carefully
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pipetted to a fresh vial, the solvent removed by evaporation, and the remaining solid
resuspended in a solution of 500 L Ag colloid, 10 L of 1 mol/L HCl, and 50 L of 0.9% NaCl. The
contents were gently mixed and measured with MISA.
This procedure converts LSD into its free base form, which is selectively solvated in DCM and
can be separated from water-soluble toner and food dye interferents.
Figure 2. LSD reference (blue), as compared with samples taken directly from colored paper and samples that have
been extracted.
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LSD on artwork blotter paper
Simulated real-life detection of LSD was conducted with commercially available sheets of
perforated artwork blotter paper. Again, 0.635 cm squares of blotter were saturated with 20 L
2
of 1 mg/mL LSD solution. Initial aqueous extraction of LSD-saturated blotter squares revealed
a complex spectrum that appeared to be a mixture of LSD and another compound (green
spectrum in
). Aqueous extraction of an untreated blotter square and library matching
Figure 3
within the Organic Chemicals v3 KnowItAll® Raman Spectral Library (Handheld) from Wiley
indicated correlation with high confidence (HQI = 0.79) to rhodamine 6G. Rhodamine 6G is a
fluorescent dye that is used in inks and sometimes as a colorant in counterfeit foods (see AN-
for more information). It is strongly Raman/SERS-active and can obscure the LSD
signal.
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Figure 3. Ultimately, comparison of experimental spectra with two references demonstrates how effective a simple
sample extraction step can be in the detection of LSD on paper substrate.
To separate LSD from rhodamine 6G, a blotter square was placed in a glass vial and shaken
with 500 L of water, next with 20 L of 1 mol/L tartaric acid, and then with 0.5 mL DCM. The
aqueous phase (top layer) was pipetted into a separate vial containing 500 L Ag colloid and 50
L 0.9% NaCl for SERS measurement. Treatment with tartaric acid results in formation of the
tartrate salt of LSD which is soluble in water and can be separated from rhodamine 6G, which
remains in the DCM layer. This simple clean-up procedure resulted in a very strong and clean
LSD signal (orange spectrum in
). This experiment demonstrates that colored
Figure 3
interferents on commercial blotter sheets may be easily removed for sensitive SERS detection
of LSD.
Extraction summary
The two procedures below illustrate the appropriate selection of solvent for the separation of
LSD from different types of colorants that may hinder detection. In a real-world scenario, a wide
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1.
2.
3.
4.
1.
2.
3.
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variety of dyes may be present. The best approach for each sample may involve
experimentation with both of extraction summaries included here:
LSD with water-soluble colorant
Shake with dilute NaOH and DCM
Carefully remove (bottom) DCM layer to a separate vial and evaporate solvent
Resuspend sample in colloid, HCl, and NaCl
Measure SERS
LSD with solvent-soluble colorant
Shake with dilute acid and DCM
Carefully remove (top) aqueous layer to a separate vial
Add colloid and NaCl
Measure SERS
Conclusion
SERS capabilities on MISA and MIRA XTR DS provide rapid onsite identification of LSD in
suspect street samples with simple, user-friendly procedures. Uniquely, this application
provides alternative extractions as a way of addressing real-world situations while keeping
sample clean-up as simple as possible. This provides a rapid and portable alternative to
conventional analytical laboratory testing procedures and their associated expenses for time,
materials, and personnel. Metrohm’s state-of-the-art test solutions continue to support
detection and regulation of illicit substances.
Metrohm AG
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9100 Herisau
Metrohm AG
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