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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

RS-014

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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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.

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