# US 10,501,432 B2 · Chiral separation of Δ8-THC, Δ9-THC, and related enantiomers using CO2-based chromatography

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- Number: US 10,501,432 B2
- Document ID: US10501432B2
- Status: Granted
- Kind: B2
- Application number: 15/473,868
- Filed: 2017-03-30
- Published: 2017-10-05
- Granted: 2019-12-10
- Earliest claimed: 2016-04-01
- Assignees: Waters Technologies Corporation
- Applicants: Waters Technologies Corporation
- Inventors: Jacquelyn Runco; Andrew Aubin; John A. Mackay
- Web page: https://patentgrep.com/patent/US10501432B2

## CPC

- C07D 311/80: Dibenzopyrans; Hydrogenated dibenzopyrans
- B01D 15/166: {Fluid composition conditioning, e.g. gradient}
- B01D 15/40: using supercritical fluid as mobile phase or eluent
- B01D 15/426: {Specific type of solvent}
- B01J 20/103: {comprising silica}
- B01J 20/24: Naturally occurring macromolecular compounds, e.g. humic acids or their derivatives
- B01J 20/28004: {Sorbent size or size distribution, e.g. particle size}
- B01J 20/29: Chiral phases
- B01J 20/3204: {Inorganic carriers, supports or substrates}
- B01J 20/3231: {characterised by the coating or impregnating layer}
- B01J 20/3293: {Coatings on a core, the core being particle or fiber shaped, e.g. encapsulated particles, coated fibers}
- B01J 2220/46: Materials comprising a mixture of inorganic and organic materials (materials coated or impregnated on a carrier B01J20/32)
- B01J 2220/54: Sorbents specially adapted for analytical or investigative chromatography
- C07B 2200/07: Optical isomers
- C07B 2200/09: Geometrical isomers
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- B01D: SEPARATION (separating solids from solids by wet methods B03B, B03D; by pneumatic jigs or tables B03B; by other dry methods B07; magnetic or electrostatic separation of solid materials from solid materials or fluids, separation by high-voltage electric fields B03C; centrifuges, vortex apparatus B04; presses per se for squeezing-out liquid from liquid-containing material B30B9/02; treatment of water C02F, e.g. softening by ion-exchange C02F1/42; {arrangements of air intake cleaners in gas turbine plants F02C7/05} ; arrangements or mounting of filters in air-conditioning, air-humidification or ventilation F24F13/28)
- B01J: CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- C07B: GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR (preparation of carboxylic acid esters by telomerisation C07C67/47; telomerisation C08F)

## Abstract

The present disclosure generally relates to methods for separating Δ8-THC, Δ9-THC, and related enantiomers using CO2-based chromatography.

## Claims

### Claim 1

A method of separating an isomer of THC selected from (+)trans-Δ8-THC, (−)trans-Δ8-THC, (+)trans-Δ9-THC, and (−)trans-Δ9-THC using CO2-based chromatography, comprising
injecting a sample comprising the isomer of THC into a CO2-based mobile phase;
flowing the CO2-based mobile phase and sample into a CO2-based chromatography system having a 150 mm length and 3 mm internal diameter column including a stationary phase disposed within the column, the stationary phase comprising modified polysaccharide-coated silica-based particles with a particle size of 2.5 μm at a rate of 2 mL/min; and
eluting the isomer of THC from the chromatography column using a mobile phase comprising CO2 and ethanol, wherein the retention time of the isomer of THC, or the first isomer of THC when multiple isomers are present, is greater than 1.5 minutes, and the total elution period of the isomer of THC, or the total elution period for the last eluted isomer of THC when multiple isomers are present, is 6 minutes or less, wherein a resolution of each pair of isomers is greater than about 2.

### Claim 2 (depends on 1)

The method of claim 1, wherein the ethanol is present in an amount ranging from 1% to 30% per total volume of the mobile phase.

### Claim 3 (depends on 1)

The method of claim 1, wherein the ethanol is present in an amount ranging from 3% to 25% per total volume of the mobile phase.

### Claim 4 (depends on 1)

The method of claim 1, wherein the ethanol is present in an amount ranging from 5% to 20% per total volume of the mobile phase.

### Claim 5 (depends on 1)

The method of claim 1, wherein the ethanol is present in an amount ranging from 5% to 15% per total volume of the mobile phase.

### Claim 6 (depends on 1)

The method of claim 1, wherein the ethanol is present in an amount ranging from 5% to 10% per total volume of the mobile phase.

### Claim 7 (depends on 1)

The method of claim 1, wherein the isomer of THC is eluted isocratically.

### Claim 8 (depends on 1)

The method of claim 1, wherein at least two isomers of THC are present in the sample and separated.

### Claim 9 (depends on 1)

The method of claim 1, wherein at least three isomers of THC are present in the sample and separated.

### Claim 10 (depends on 1)

The method of claim 1, wherein each of (+)trans-Δ8-THC, (−)trans-Δ8-THC, (+)trans-Δ9-THC, and (−)trans-Δ9-THC are present in the sample and separated.

### Claim 11 (depends on 1)

The method of claim 1, wherein the retention time of the isomer of THC, or the first isomer of THC when multiple isomers are present, is greater than 1.7 minutes.

### Claim 12 (depends on 1)

The method of claim 1, wherein the total elution period of the isomer of THC, or the total elution period for the last eluted isomer of THC when multiple isomers are present, is 5.5 minutes or less.

### Claim 13 (depends on 1)

The method of claim 1, wherein the total elution period of the isomer of THC, or the total elution period for the last eluted isomer of THC when multiple isomers are present, is 5 minutes or less.