Small Molecule Purification

More Product. Less Solvent. MCSGP for Nutraceuticals.

Higher yield, no re-chromatography. MCSGP continuous polishing for cannabinoids, omega-3 fatty acids, steviol glycosides, flavonoids, and beyond — same RP-HPLC chemistry, same C18 columns, same solvents you already use. │ 52% → 94% CBD yield at ≤100 ppm THC │ 7.5× Productivity at equivalent purity │ –30% Solvent consumption

Source: YMC ChromaCon Application Note (CBD purification from hemp extract, RP-HPLC)

Talk to Our Small Molecule Specialists

Download the CBD Application Note

Talk to Our Small Molecule Specialists

Download the CBD Application Note

The Natural Extract Purification Problem

Demand for high-purity nutraceutical actives — pharmaceutical-grade CBD, ultra-pure EPA from fish oil, high-intensity sweeteners, botanical polyphenols — is growing rapidly. Chromatographic polishing is typically the final and most critical purification step. It must deliver both high purity and high yield from complex, variable natural extract feeds.

Conventional batch RP-HPLC forces an impossible choice: hit purity specifications or recover maximum yield — not both. Natural extracts contain structurally similar co-eluting compounds (e.g., CBD with THC, EPA with DHA, Rebaudioside A with other steviol glycosides) that form the very impurity profile a center-cut must navigate. Narrow cuts achieve purity but sacrifice yield; wide cuts maximize recovery but fail purity specifications.

The result: low-yield batch runs, costly re-chromatography, high solvent consumption, and excessive QC testing — all compressing margins in an already cost-sensitive market.

The Solution: MCSGP with AutoPeak® for Small Molecule Polishing

MCSGP (Multi-column Countercurrent Solvent Gradient Purification) eliminates the purity-yield trade-off in small molecule and nutraceutical chromatography. Two identical reversed-phase columns continuously recycle impure side-fractions — recovering target compound that batch processes discard. It uses the same RP stationary phases, solvents, and gradients as your existing batch method.

AutoPeak® dynamic process control monitors the elution profile in real-time via UV, automatically adjusting collection windows to maintain consistent purity output — enabling robust, unattended 24/7 operation even when feed composition varies from batch to batch.

Same chemistry. Dramatically better results. MCSGP uses the same reversed-phase C18/C8 resins, organic solvents, and gradient methods already used in your batch small molecule process — these existing conditions are the starting point for MCSGP development. No change to your resin or solvent chemistry is needed.

Learn About MCSGP + AutoPeak®

Proven Results: MCSGP vs. Batch Chromatography

+80%

CBD Yield Increase (at 100 ppm THC)

7.5×

Productivity Increase (at 1000 ppm THC)

+250%

EPA-EE Yield Increase

6×

EPA-EE Productivity Increase

+334%

Crocin-I Recovery Increase

Case Study 1: CBD Purification from Hemp Extract

Molecule: Cannabidiol (CBD) from hemp plant extract; delta-9 THC as critical regulated impurity Equipment: Contichrom CUBE Mode: RP-HPLC

Parameter	Batch RP-HPLC	MCSGP
CBD Yield (at 100 ppm THC spec)	52%	94% (+80%)
Productivity (at 1,000 ppm THC spec)	Baseline	7.5× higher
THC reduction (at same productivity as batch)	1,000 ppm	100 ppm (10-fold)
Solvent consumption	Baseline	−30%
QC samples per run	Multiple fractions per injection	1 per MCSGP cycle
Method setup time	N/A (existing method)	<15 min (ChromIQ® MCSGP Wizard)

Key finding: MCSGP recovered nearly all CBD discarded in batch side-fractions, achieving 94% yield at the 100 ppm THC pharmaceutical limit — versus 52% by batch. Operating at the same productivity as batch, MCSGP alternatively delivers a 10-fold reduction in THC content with no productivity penalty. Process parameters were configured in under 15 minutes from a single existing batch chromatogram.

ChromaCon Application Note P2.V3 (2024). chromacon.com

Case Study 2: EPA-EE Purification from Fish Oil

Molecule: Eicosapentaenoic acid ethyl ester (EPA-EE) from generic fish oil; DHA-EE as principal co-eluting impurity. Feed purity: 74% EPA-EE. Target: >97% EPA-EE purity. Equipment: Contichrom CUBE Mode: RP-HPLC (5 MCSGP cycles)

Parameter	Batch RP-HPLC	MCSGP
Yield (at >97% EPA-EE purity)	Baseline	+250%
Productivity	Baseline	+590% (>6× throughput per column volume per hour)
Solvent consumption	Baseline	−75%

Key finding: The near-identical RP-HPLC retention of EPA-EE and DHA-EE (both 20-carbon omega-3 fatty acids differing only in degree of unsaturation) makes this a separation where batch chromatography forces extreme center-cuts. MCSGP’s internal recycling unlocks this challenging separation: five cycles delivered +250% yield, +590% productivity, and 75% less solvent — from the same columns and mobile phases used in batch.

ChromaCon/Knauer EPA-EE Purification from Fish Oil with MCSGP. Application note data (2013), Currently unavailable for download.

Case Study 3: Crocin-I Purification from Saffron Extract

Molecule: Crocin-I (trans-crocetin di-(β-D-gentiobiosyl) ester) from saffron (Crocus sativus L.) stigma extract; feed purity 27%; co-eluting crocin structural analogs as impurities Equipment: Contichrom CUBE (Chromacon YMC, Zurich, Switzerland) Mode: RP-HPLC — green process using only ethanol/water (no acetonitrile or additives); Daisogel-SP-120-10-C18-Bio, 10 µm

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Parameter	Batch (25 cm column)	MCSGP (2 × 15 cm columns)	Intensification
Purity	99.7 ± 0.0%	99.7 ± 0.1%	Identical
Recovery (Yield)	21.9 ± 0.2%	95.1 ± 1.0%	+334%
Productivity	1.4 ± 0.0 g/L/h	5.7 ± 0.5 g/L/h	+307%
Solvent consumption	46.4 ± 0.0 L/g	3.5 ± 0.0 L/g	−92%

Key finding: Application of MCSGP to the purification of a natural product from a complex plant extract. The structural similarity among crocin variants creates a batch yield-purity dilemma identical to that seen in pharmaceutical separations — only 21.9% of crocin-I was recoverable by batch at 99.7% purity. MCSGP resolved this completely, recovering 95.1% at the same purity — a 334% increase — while simultaneously improving productivity 3-fold and cutting solvent consumption by 92%. Notably, ethanol was the sole organic solvent, demonstrating that MCSGP process intensification and green chemistry principles are fully compatible. Steady state was achieved from the second MCSGP switch across all 5 cycles.

Hooshyari Ardakani, M., Nosengo, C., Felletti, S. et al. Anal. Bioanal. Chem. (2024). DOI: 10.1007/s00216-024-05228-6

Nutraceutical Purification Comparison Table:

Parameter	Batch RP-HPLC	MCSGP with AutoPeak®
Purity-Yield Trade-off	Inherent — narrow cuts sacrifice yield	Eliminated — high purity AND high yield simultaneously
Product Yield	50–70% (typical for complex extracts)	80–97%+ (depending on separation difficulty)
Re-chromatography	Required for side-fractions	Eliminated — internal recycling
Solvent Consumption	High	30–75% reduction
Productivity	Baseline	Up to 7.5× higher
QC/IPC Burden	Multiple fractions per batch, extensive testing	One sample per cycle — massive reduction
Design Time	N/A (existing method)	MCSGP method from batch chromatogram in <15 min
Feed Variability Handling	Manual re-optimization required	AutoPeak® compensates automatically
Scalability	Limited by column size	Linear scale-up through Contichrom platform

The Contichrom® Platform: From Lab to Production

All three systems run MCSGP with AutoPeak® and ChromIQ® software. Methods scale predictably from CUBE → PILOT 300X → TWIN HPLC.

System Overview

Contichrom® CUBE

The essential platform for chromatography process development. This versatile 100-bar benchtop FPLC system runs batch, integrated batch, and continuous chromatography — including MCSGP and CaptureSMB — out of the box. Develop purification processes for mAbs, peptides, oligonucleotides, ADCs, and viral vectors, with verified scale-up at over 100× to pilot and production systems.

Contichrom® PILOT

Scale peptide and oligonucleotide purification to pilot and clinical GMP manufacturing. This 100-bar preparative HPLC system features MCSGP with AutoPeak® to eliminate the yield-purity trade-off — delivering +10–50% absolute yield increase at target purity and significantly less solvent than batch HPLC. ATEX Zone 2 / Class I Div 2 certified for organic solvents. Flow rates up to 300 mL/min.

Contichrom® TWIN HPLC

Produce peptides and oligonucleotides at commercial GMP scale. This 80-bar industrial HPLC system uses MCSGP with AutoPeak® to eliminate the yield-purity trade-off — increasing recovery to >90% while reducing solvent consumption compared to batch. ATEX Zone 2 / Class I Div 2 certified for organic solvents, and flow rates up to 36 L/min.

System Overview

Applications Across Natural Product Categories

Use Case 1: Cannabinoids (CBD, CBG, CBN)

Remove regulated impurities including delta-9 THC, delta-8 THC, and other cannabinoid co-eluters from hemp extract. Meet pharmaceutical- and food-grade purity specifications at dramatically higher yield. Key result: +80% CBD yield at 100 ppm THC specification.

Use Case 2: Omega-3 Fatty Acids (EPA, DHA)

Purify high-value omega-3 ethyl esters (EPA-EE, DHA-EE) from complex fish oil matrices to pharmaceutical-grade (≥97%) purity. Separate EPA from DHA despite near-identical RP-HPLC retention. Key result: +250% yield, +590% productivity, 75% less solvent.

Use Case 3: Steviol Glycosides (Rebaudioside A, Reb M, Reb D)

Isolate individual high-intensity steviol glycosides from Stevia leaf extract or fermentation broth. Separate closely related glycoside variants at high purity for use in next-generation sweetener formulations.

Use Case 4: Carotenoids & Botanical Pigments (Crocin-I, Crocetin Esters, Lutein)

Structural similarity among crocin variants makes saffron extract a classic batch-impossible separation. MCSGP purified crocin-I from saffron to 99.7% purity at 95.1% recovery — a 334% improvement over batch — using only ethanol/water. Published proof-of-concept for this class; Hooshyari Ardakani et al. 2024

Applications Across Natural Product Categories Continued….

Use Case 5: Flavonoids & Polyphenols

Purify quercetin, rutin, resveratrol, curcuminoids, and similar polyphenolic actives from botanical extracts. Resolve closely related structural isomers and glycoside variants in a single continuous polishing step.

Use Case 6: Chiral Small Molecules & Pharmaceutical Intermediates

Extend MCSGP to chiral preparative separations and pharmaceutical small molecule API polishing — any separation currently performed by gradient batch RP-HPLC, including standard and chiral stationary phases.

Use Case 7: Fermentation-Derived Actives

Purify bioactive compounds from fermentation broth purification trains — vitamins, amino acid derivatives, terpenoids, alkaloids — where complex co-product profiles challenge conventional batch chromatography.

Getting Started with MCSGP for Nutraceuticals and Small Molecules

See the Contichrom® platform in action before you commit, then assess MCSGP suitability for your RP-HPLC purification — computationally from your existing batch data, or experimentally at YMC ChromaCon’s Zurich facility. Develop your continuous method at lab scale on a Contichrom CUBE, then scale to the PILOT 300X or TWIN HPLC for high-throughput or tonne-scale production.

See It First — Free Demo or Webinar

Not yet familiar with the Contichrom® platform? Start here. YMC ChromaCon offers no-charge demonstrations and introductory webinars tailored to your team.

On-site in Zurich (half day, 2–4 hours): see the CUBE in person, run ChromIQ® live, discuss your small molecule or nutraceutical purification challenge with ChromaCon application scientists
Remote webinar (1–3 hours): interactive live session covering MCSGP, N-Rich, ChromIQ® software, and the full Contichrom® ecosystem
Sessions cover MCSGP for RP-HPLC separations, the ChromIQ® MCSGP Wizard, and scale-up to PILOT 300X and TWIN HPLC

→ Request a free demo or introductory webinar

Modeling Assessment for Nutraceuticals

Predict how MCSGP will perform on your small molecule or nutraceutical purification before running any new experiments. YMC ChromaCon evaluates MCSGP suitability using mechanistic modeling from your existing batch RP data.

Submit your batch RP-HPLC method details — chromatogram, gradient, resin or stationary phase, column dimensions — and any available fraction analysis data; from any HPLC or FPLC system, no Contichrom® required
YMC ChromaCon evaluates MCSGP suitability and estimates expected yield, purity, and throughput improvements versus your current batch process — typically starting from your analytical RP-HPLC chromatogram alone
Typical timeline: 3–5 weeks from receipt of data; no material shipment required

→ MCSGP Process Modeling Service

Experimental Feasibility Study — Your Compound, Your Resin

Your compound, API, or extract is purified on YMC ChromaCon’s Contichrom® platform at our facility in Zurich. We reproduce your batch RP method as a benchmark and run ≥ 3 MCSGP experiments side-by-side.

Ship starting material to Zurich — typically ≥ 20× a single preparative batch run, scaled to 1 cm i.D. columns
We reproduce your analytical HPLC method, establish the batch benchmark, and run MCSGP experiments using your resin and solvent system
Deliverable: side-by-side batch vs. MCSGP comparison with real chromatographic data from your compound, plus fractions for your independent purity verification
Typical timeline: 4–6 weeks after receipt of starting material and purchase order

→ YMC ChromaCon Feasibility Studies

Develop at Lab Scale — Rent or Purchase a CUBE

MCSGP method development is performed on the Contichrom CUBE using your existing RP resin and mobile phase system. Available for rental or purchase.

ChromIQ® MCSGP Wizard designs the initial MCSGP operating point from a single batch chromatogram — method setup completed in approximately 15 minutes
Your current batch gradient conditions are the starting point — no new resin or mobile phase development required
AutoPeak® dynamic process control adjusts collection windows in real-time via UV monitoring, compensating for feed concentration variability and column conditioning changes
N-Rich® impurity enrichment can also be run on the same CUBE platform if impurity isolation or reference standards are needed alongside process development

→ Contichrom® CUBE Rental Program

→ Purchase a Contichrom® CUBE

Scale to Production — PILOT 300X or TWIN HPLC

The MCSGP method developed on the CUBE transfers directly to larger Contichrom systems for pilot, pharmaceutical-grade, and high-volume manufacturing. YMC ChromaCon provides scale-up consulting and GMP documentation support.

PILOT 300X (up to 300 mL/min, 100 bar, ATEX Zone 2) for pilot-scale batches and clinical or commercial scale-up trials — the same ATEX-certified platform used across pharmaceutical small molecule and API manufacturing
TWIN HPLC for large-scale continuous production, including tonne-scale output for high-volume nutraceutical and commodity API manufacturing
Scale-up is driven by column diameter — bed height, gradient conditions, and AutoPeak® control logic are preserved across scales
GMP documentation support (IQ/OQ/PQ) and scale-up consulting available where required for pharmaceutical-grade production

→ Scale-Up Consulting and Training

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Ready to Increase Your Small Molecule or Nutraceutical Yield?

What types of nutraceutical compounds can MCSGP purify?

Any compound currently purified by gradient reversed-phase HPLC is a strong MCSGP candidate. This includes cannabinoids, omega-3 fatty acid esters, steviol glycosides, flavonoids, polyphenols, carotenoids, terpenes, and fermentation-derived bioactives. The more structurally similar the target and its co-eluting impurities, the greater the benefit MCSGP delivers.

How does MCSGP improve CBD yield while meeting THC limits?

Batch RP-HPLC requires a narrow center-cut to stay below the 100 ppm THC limit — discarding valuable CBD in impure flanking fractions. MCSGP continuously recycles those side-fractions, re-separating CBD from THC in the second column. The result: 94% CBD yield vs. 52% with batch, at the same 100 ppm THC specification.

Why are the gains so large for omega-3 EPA purification?

EPA and DHA are structural analogs with nearly identical RP-HPLC retention — a classic difficult ternary separation where batch chromatography forces extreme center-cuts. MCSGP’s internal recycling is specifically designed to unlock these challenging separations, delivering +250% yield and +590% productivity from the same columns and solvents.

Does MCSGP require changing my existing RP-HPLC method or resin?

No. MCSGP uses the same reversed-phase (C18, C8) stationary phases, organic solvents (e.g., methanol, ethanol, acetonitrile/water), and gradient profiles as your existing batch method. The ChromIQ® MCSGP Wizard designs the MCSGP run directly from your batch chromatogram — typically in under 15 minutes.

Can the Contichrom CUBE system operate in Normal Phase mode?

How does MCSGP handle variable natural extract feedstocks?

Natural extract composition can vary between harvest batches, seasons, or suppliers. AutoPeak® dynamic process control monitors real-time UV signal and automatically adjusts collection and recycling cut points — maintaining consistent product purity even when the feed profile shifts. No manual re-optimization is needed between campaigns.

How does MCSGP reduce solvent consumption?

Because side-fractions are internally recycled rather than discarded and re-processed, total solvent throughput per gram of purified product drops sharply. For omega-3 EPA purification, MCSGP reduced solvent consumption by 75% vs. batch. For CBD, a 30% reduction was demonstrated. Less solvent means lower purchase, regeneration, and disposal costs — significant at commercial scale.

What scale of production is supported?

The Contichrom platform scales from lab (CUBE, 0.1–100 mL/min) through pilot (PILOT 300X) to full manufacturing scale (TWIN HPLC). The TWIN HPLC is the standard production system for reversed-phase HPLC applications including nutraceuticals and small molecules. GMP-grade TWIN systems operate at flow rates suitable for tonne-scale annual production. MCSGP process parameters developed on the CUBE transfer predictably across scales.

Can Contichrom systems also run conventional batch chromatography?

Yes. All Contichrom systems support batch, 2D/3D integrated batch, and continuous MCSGP modes on the same hardware. TWIN production systems are dual-mode — so you can run batch and MCSGP on the same skid without separate equipment, enabling a flexible mixed-mode production facility.