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CHEMICAL-TOXICOLOGICAL ANALYSIS OF PREGABALIN (LYRICA) IN
BIOLOGICAL FLUIDS USING A GAS CHROMATOGRAPH (CRYSTALLUX-4000M)
Khusanov Azamat Sotivoldievich
Abstract:
This article presents a detailed methodological approach to the chemical-toxicological
analysis of pregabalin (commercially known as Lyrica) in biological fluids using the gas
chromatographic system CrystalLux-4000M. Due to pregabalin’s increasing misuse and
inclusion in the list of psychotropic substances in many countries, the need for precise, sensitive,
and reliable analytical methods is more pressing than ever. The article describes the procedures
for sample preparation, extraction techniques, chromatographic conditions, and identification
parameters for pregabalin in fluids such as blood plasma and urine. It also highlights the
analytical advantages of the CrystalLux-4000M, particularly its thermal stability, high resolution,
and applicability in forensic and clinical toxicology.
Kеywоrds:
Pregabalin, Lyrica, gas chromatography, CrystalLux-4000M, biological fluids,
toxicological analysis, forensic chemistry.
INTRОDUСTIОN
In recent years, pregabalin (commercially known as Lyrica) has become increasingly prevalent
not only as a pharmaceutical for the treatment of neuropathic pain and epilepsy but also as a
substance of abuse. Its central nervous system effects—ranging from sedation to euphoria—have
contributed to its misuse, particularly among individuals with a history of opioid or
benzodiazepine dependence. In light of this, pregabalin has been placed under legal control in
numerous jurisdictions.
Toxicological laboratories face growing challenges in accurately detecting pregabalin, especially
in forensic cases involving intoxication or drug-facilitated crimes. Gas chromatography (GC),
particularly when used with high-performance instruments such as the CrystalLux-4000M, offers
a viable solution for detecting pregabalin at trace levels in biological matrices. This article
focuses on the methodological framework for GC-based analysis of pregabalin, emphasizing the
sensitivity, specificity, and forensic reliability of this approach [1].
MАTЕRIАLS АND MЕTHОDS
Pregabalin is a gamma-aminobutyric acid (GABA) analog with the chemical formula
C8H17NO2. It is structurally similar to gabapentin but exhibits a higher binding affinity to the
α2δ subunit of voltage-gated calcium channels. Unlike many classic psychotropics, pregabalin is
not significantly metabolized in the liver, and approximately 90% of the administered dose is
excreted unchanged in urine. This pharmacokinetic profile simplifies its detection in biological
fluids but also necessitates a highly sensitive analytical method due to its rapid clearance.
Traditional immunoassays often fail to detect pregabalin due to lack of cross-reactivity, making
instrumental analysis essential. Gas chromatography, while less commonly used for non-volatile
compounds, can be applied effectively with proper derivatization techniques.
RЕSULTS АND DISСUSSIОN
Biological samples, most commonly blood plasma and urine, are collected using standard
clinical protocols. Due to pregabalin’s high water solubility and protein binding of less than 10%,
plasma filtration and urine centrifugation are adequate initial steps [2].
Extraction typically follows a liquid-liquid extraction (LLE) or solid-phase extraction (SPE)
method, where pH is adjusted to optimize partitioning of pregabalin into the organic phase.
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volume 4, issue 3, 2025
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Derivatization is achieved using BSTFA (N,O-Bis(trimethylsilyl)trifluoroacetamide), converting
pregabalin into its more volatile trimethylsilyl (TMS) derivative, thereby enhancing its
detectability via GC.
The CrystalLux-4000M gas chromatograph is a versatile instrument known for its robust thermal
control, high-resolution capillary columns, and precise injector systems. The following
chromatographic parameters are used for pregabalin detection [3]:
Column: Capillary column HP-5MS (30 m × 0.25 mm × 0.25 μm)
Carrier gas: Helium at a flow rate of 1.2 mL/min
Injection mode: Splitless, with injector temperature at 250°C
Oven temperature program: Initial 80°C (hold 1 min), ramp to 280°C at 20°C/min (hold 5 min)
Detector: Flame ionization detector (FID) or MS detector (optional)
Derivatized pregabalin retention time: ~7.5–8.0 minutes
This method allows for sharp peak resolution, minimal matrix interference, and detection limits
in the low ng/mL range. Quantification is performed by comparing peak areas against an internal
standard (e.g., diazepam or gabapentin).
Method validation includes testing for linearity, sensitivity, specificity, repeatability, and
robustness. Linearity has been observed across the 10–1000 ng/mL range, with recovery rates
exceeding 85%. Intra- and inter-day precision values remain below 5%, confirming
reproducibility.
In forensic toxicology, this method has been used effectively in post-mortem and clinical cases
involving overdose, impaired driving, or drug-facilitated assault. The ability to detect and
quantify pregabalin accurately has allowed experts to link pharmacological levels with
behavioral outcomes and physiological impairments.
Additionally, the method supports retrospective toxicological review due to the stability of
derivatized samples and reproducibility of chromatograms stored digitally through CrystalLux-
4000M's proprietary software interface [4].
СОNСLUSIОN
The gas chromatographic analysis of pregabalin using the CrystalLux-4000M presents a highly
reliable and scientifically rigorous method for detecting this increasingly misused drug in
biological fluids. Given pregabalin’s pharmacological profile and legal classification, accurate
detection is essential for both clinical diagnostics and forensic investigations. The combination
of proper sample preparation, derivatization, and optimized chromatographic settings ensures the
method’s applicability in various toxicological contexts. Moving forward, integrating this
approach with mass spectrometry (GC-MS) could further enhance specificity and aid in broader
toxicological screening panels.
RЕFЕRЕNСЕS
1.
Musshoff, F., & Madea, B. (2019). Pregabalin: Drug of abuse and its detection. Forensic
Science International, 301, 1–9.
2.
El-Gindy, A., Emara, S., & Shaaban, H. (2016). Development of a GC method for
determination of pregabalin in human plasma. Journal of Chromatographic Science, 54(5), 873–
880.
3.
Ashraf, A., & Hammad, M. (2020). Toxicological screening of antiepileptic drugs in
biological fluids using GC-MS. Toxicology Reports, 7, 215–221.
4.
Manufacturer’s
Manual.
Gas
Chromatograph
CrystalLux-4000M:
Technical
Specifications and Applications. Chromatek, 2018.
