Literature Statistics 2000-2007

From TheLiquidPhase

Survey of Countercurrent Separation Literature from 2000-2007

Introduction and Rational

Documenting difference between theory and practice.

Understanding best-practices.

Understanding (perceived) strengths and weaknesses of Countercurrent Separation.

Looking for directions for further research.

Literature:

Journals and articles surveyed:

A survey was conducted with a set of 138 journal articles. Journal articles chosen for survey described the isolation and characterization of natural products with a CS experiment as one or more of the chromatographic steps. Articles that describe natural product isolation rather than instrument design, method development, operational design, or the separation of synthetic or inorganic chemicals comprise about 43% of the literature from 2000 through 2007 [Scifinder search and printout with subsequent manual proofreading].

Bibliography

The majority of articles are from two journals: the Journal of Chromatography A, 40, and Journal of Liquid Chromatography and Related Technologies, 32. The remainder of articles is from 22 journals during the time span of 2000 through 2007.

Journals

Details of Survey:

Articles “interrogated” to glean a variety of information. Used three different formats 1) yes/no questions, 2) values, and 3) descriptions. Both yes/no questions and values are quantifiable. The descriptions supply information needed to embellish yes/no questions and values.

Survey Format

Results:

Solvent System Selection:

A total of 187 solvent systems where used.

A total of 665 individual solvents were used.

29% used a solvent system of the hexane-ethyl acetate-methanol-water family to perform the featured liquid-liquid separation.

18% used a solvent system that resembles the hexane – ethyl acetate – methanol – water with a single substitution (also called 1st generation hexane-ethyl acetate-methanol-water solvent system family).

20% of the solvent systems were modified with organic or inorganic solutes.

Table: solutes

Six solvent systems were non-aqueous in nature.

49% of articles describe, in some depth, how the solvent systems employed in the separation were selected. Many of these articles include a table detailing the list of solvent systems used in shake-flask experiments and the corresponding K values of the target analyte(s).

Of those articles that gave a description of solvent system selection, there were an average of 3.0 solvent system families investigated and 8.5 solvent systems per article.

Terms:

“K” not mentioned 46%
“K”used as symbol to represent “partition coefficient” 48% of articles.

Different symbol used for “K” in 6% of articles

“Partition coefficient” or related term not used in 45% of articles.
“Partition coefficient” used in 50% of articles.

Chromatograms

70% of the articles include at least one CS chromatogram.

Of those articles with chromatograms, 95% of them used a unit of time on the x-axis.
Time was not used in four articles, instead, volume was chosen as the x-axis unit.
Fisher 2005, JLCRT; Maciuk 2005 JLCRT; Lui 2006 SPT vol. 52; Liu 2007 Talanta vol. 71

The most common y-axis units were absorption.
Five articles used ELSD detection rather than UV-vis.
Yao 2006 JCA vol. 1139; Tang 2007 JCA vol. 1144; Ha 2007 JCA vol. 1151; Shi 2007 JCB vol. 852; Liu 2007 Talanta vol. 71

Parameters independent of sample:

74% of CS experiments were done under with the hydrophilic phase mobile (reversed-phase).

Only 57% of the articles recorded the stationary phase retention ratio (Sf).
Fortunately, Sf can be estimated from most chromatograms.

80% of the articles, describe CS as the final purification step.

Sample parameters:

92% of articles report on the sample mass loaded on the CS column.

Frequency of Column Loading

80% of the articles report on the mass of compound recovered.

The sample enrichment ratio can be calculated from by dividing the mass of compound recovered by the mass of sample loaded. In natural products, sample enrichment is an important piece of information because not only do extracts contain a large number of compounds, these compounds are present in widely varying proportions. In general, it is easier to isolate a major component or active fraction (low enrichment) from a mixture than to isolate a minor component or active fraction (high enrichment). In the articles surveyed, the enrichment of a target compound range from greater than 200 to less than 2. The average enrichment was on the order of 27-fold.

21% of the articles report on the percentage product recovered (mass of compound in sample loaded times 100/ mass of compound recovered).
In CS percent recovery is often high (> 90%).

Only 6% of articles report on the CS experimental K value of compounds recovered {K = (VR-VM)/VS}.

Fortunately, in articles with published chromatograms, K can be estimated from the retention time, together with flow rate, stationary phase retention ratio, and column volume.

image: freq_K

72% of articles report on the percent purity of isolated compounds.
The purity of isolated compounds is invariably reported to be greater than %95 when the CS step is the final step of the purification process.

32% of articles report the isolation of a single natural product.
The average number of compounds isolated per article is 3.5.

Only 11% of target compounds are reported as being “novel” (if “novel” means a new natural product or new to the species is not always clear).

Instruments:

88% of the instruments used were identified as hydrodynamic J-type centrifuges.

Hydrostatic CPC --> Rhee 2004 BPB; Hazekamp 2004 JLCRT vol. 27; Macuik 2005 JLCRT vol. 28; Renault 2006 JLCRT vol. 29; Kim 2006 JLCRT vol. 29; Shirota 2007 JLCRT vol. 30; Delaunay 2002 JCA vol. 964; Pinel 2007 JCA vol. 1151; Bringmann 2005 Journal of Natural Products p. 686.

Slow Rotation CCC (SRCCC)--> Zhao 2007 JCA vol. 1151; Du 2006 JLCRT vol. 29, Du 2007 JLCRT vol. 30.

table: instruments

Frequency of Instrument Volumes

60% of articles reported the βr range for J-type instruments.

36% of the CCC articles report on the temperature of separation.

31% of the articles performed a preliminary column chromatography step prior to the CS experiment.