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Rapid isolation procedure for Δ9-tetrahydrocannabinolic acid A (THCA) from Cannabis sativa using two flash chromatography systems.

By July 29, 2013No Comments

pm2Rapid isolation procedure for Δ9-tetrahydrocannabinolic acid A (THCA) from Cannabis sativa using two flash chromatography systems.


Institute of Forensic Medicine, University Medical Centre Freiburg, Albertstrasse 9, 79104 Freiburg, Germany.


Two isolation procedures for Δ9-tetrahydrocannabinolic acid A (THCA), the biogenetic precursor in the biosynthesis of the psychoactive Δ9-tetrahydrocannabinol (THC) in the cannabis plant, are presented. Two flash chromatography systems that can be used independently from each other were developed to separate THCA from other compounds of a crude cannabisextract. In both systems UV absorption at 209 and 270 nm was monitored. Purity was finally determined by HPLC-DAD, NMR and GC-MS analysis with a focus on the impurity THC. System 1 consisted of a normal phase silica column (120 g) as well as cyclohexane and acetone–both spiked with the modifier pyridine–as mobile phases. Gradient elution was performed over 15 min. After the chromatographic run the fractions containing THCA fractions were pooled, extracted with hydrochloric acid to eliminate pyridine and evaporated to dryness. Loading 1800 mg cannabis extract yielded 623 mg THCA with a purity of 99.8% and a THC concentration of 0.09%. System 2 was based on a reversed-phase C18 column (150 g) combined with 0.55% formic acid and methanol as mobile phases. A very flat gradient was set over 20 minutes. After pooling the THCA-containing fractions methanol was removed in a rotary evaporator. THCA was re-extracted from the remaining aqueous phase with methyl tert-butyl ether. The organic phase was finally evaporated under high vacuum conditions. Loading 300 mg cannabis extract yielded 51 mg THCA with a purity of 98.8% and a THC concentration of 0.67%.
Copyright © 2011 Elsevier B.V. All rights reserved.
[PubMed – indexed for MEDLINE]


► Tetrahydrocannabinolic acid A is the biogenetic precursor of THC in the Cannabis plant. ► We present an isolation procedure for THCA with two flash chromatography systems. ► System 1 runs on normal phase, system 2 on reversed phase columns. ► Purity was tested with HPLC-DAD and GC–MS analysis, identity confirmed with NMR. ► The methods are rapid, do not use harmful solvents and yield purity grades >98.8%.


  • Δ9-Tetrahydrocannabinolic acid A;
  • Isolation;
  • Flash chromatography

Figures and tables from this article:

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Fig. 1. Structures of Δ9-tetrahydrocannabinolic acid A (THCA) and Δ9-tetrahydrocannabinol (THC).
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Fig. 2. Chromatogram of a run with normal phase silica gel (mobile phase A: cyclohexane containing 0.1% pyridine, mobile phase B: mobile phase A and acetone 2:1).
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Fig. 3. Chromatogram of a run with reversed phase silica gel (mobile phase A: 0.55% formic acid, mobile phase B: methanol), A–D: minor impurities.
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Fig. 4. (A) Quantification of THCA with HPLC-DAD: chromatogram of a sample of isolated THCA (c = 100 μg/mL) containing 50 μg 11-OH-THC, injection volume: 10 μl. (B) Quantification of THC with HPLC-DAD: sample of isolated THCA (c = 1 mg/mL) containing 25 μg 11-OH-THC, injection volume: 20 μl, calculated THC concentration 0.67%.
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Fig. 5. GC–MS analysis: chromatogram of a sample containing 10 μg/mL isolated THCA, Sil: peaks that were also found in a blank sample containing MSTFA and ethyl acetate.
Corresponding author contact information
Corresponding author. Tel.: +49 761 203 6849; fax: +49 761 203 6858.

Copyright © 2011 Elsevier B.V. All rights reserved.
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