Document N21yooJ9dkDBDgk8QRGaRJM7p

To: Copies to: R. J, Abramowitz C. IV, Corbin L. J. Friedman B. P. Hirsch W. D. Howells H. 11. Raster W. Tybus Subject: GC RECENT ARTICLES INTER-OFFICE MEMORANDUM File Ref.: RVL:398-73M Date: June 20, 1973 From: R. V. Lucke Div./Dep't: RUCO/Polymers Location: Burlington Attached are several recent articles on GC utilization. Pages 34 and 42 have reasonable summaries for general review. I thought you might be interested in view of our heavy recent involvement in VCM quality and the FDA problem. RVL/cmc OCC 1716 f l-R UP-DATE HPLC (Liquid Chromatography) state of ihe art 1973 he analytical technique of chromatog the sample is separated into its components, Traphy is, by any standard, one of the which emerge from the'end of the column at most powerful that has ever been developed.different times, and pass through a suitable Almost every analytical laboratory--and cer detector. tainly any laboratory that is concerned with Liquid column chromatography has been the analysis of organic materials (including, of course, those in the life sciences)--is equipped with some form of chromatographic understood in principle for at least 50 years, but until recently suitable equipment, particularly pumps and detectors, has not instrumentation. It may be a gas chromato been available. graph or the equipment to perform thin layer A typical liquid chromatographic column is or paper chromatography. 500 mm long, has an inside diameter of about And now increasing interest is being shown 2 mm, and is packed with spheres 10 to 30 in liquid column chromatography, also known microns in diameter. Unless high-pressure as high pressure liquid chromatography pumps are employed, the elution of a sample (HPLC). This was known formerly as liquid from such a column would take many hours chromatography, but researchers prefer a or even days. morc-prccisc term since other techniques also Now, however, it is common to use pump involve liquid in the process. pressures of 1,000 to 3,000 psi (70 to 220 HPLC, the major subject of this article, has kg/cm2) and constant-flow pumps capable of the curious distinction of being at once the 7,000 psi (500 kg/cm2) have recently been oldest and the newest of the chromatographic introduced. With such pumps, an analysis techniques. In its simplest form, IIPLC can be can be completed in several minutes. regarded as an increase in the sophistication A typical sample size for a high pressure of paper and thin layer techniques. liquid chromatograph is 10 to 20 /d, while sol Tlie sample is injected into a chromato vent flow rates arc of the order of 0,5 to 5 ml graphic column through which a suitable per minute. It requires only a simple compu solvent is being pumped. Inside the column, tation to lead to the conclusion that the diIn- OCC 1717 INDUSTRIAL RESEARCH--JUNE 1973 tion of tlie sample is very great, placing great J ,1,, * l-v . r 1 / . I ' /-`f (\-r- ,3 +- fK 1 of the chionialographic column. At present tun types of detectors, RI and UV, arc in general use. The refractive index detector measures differences in the optical refractive index, comparing the refractive index of the pure solvent to that of solvent plus sample. The Output of the detector appears as a recorder peak where the area depends on the concentration of the sample component being measured, as well as on the difference between the refractive indices of the solvent and the sample component. Until recently, refractive index detectors had mystifying problems and irritating in stabilities. Now, however, detectors are available which can reliably measure differ ences of 10-s units in refractive index. (As a standard of comparison, the refractive index of a vacuum is defined as 1.0, while that of ordinary window glass is approximately 1.5.) Most materials have the ability to absorb radiation at ultraviolet wavelengths. Therefore an alternative detector, which frequently is used in HPLC, is an ultraviolet spectropho tometer. Since, again, tiny absorbances must be measured, the spectrophotometer that is used most commonly is a double-beam unit (for stability), employing a filter with a band pass that peaks near 250 nm (for compactness liquid chromatography is only starting to come into routine use in solvinr nnalvt;cal problems, ltirt of tile reason is that it lias not been long since pumps and detectors have been brought under control, and it is even more recently that it has been possible to produce reliable and repeatable column packing materials. The latter is of extreme importance. Un less column packing materials are under good control, it is not possible to repeat with one instrument on one day an analysis that has been published on the basis of work done on another instrument on another day. Another reason for the delayed acceptance is, paradoxically enough, the bewildering variety of opportunities that are open in high pressure liquid chromatography. Essentially, there are four different techniques possible: liquid-liquid chromatography, described earlier, which is known as partition; liquidsolid chromatography, where the substrate is a solid, and which therefore depends on selec tive adsorption; molecular exclusion, which represents an upgrading of gel permeation chromatography; and the well-known tech nique of ion exchange. Furthermore, there is an almost infinite choice of solvents and substrates. However, even now a substantial body of applications is emerging for which modem W V6 i\ J Q l!F ` SINjSMPCS COLUMN SAMPLE CELL DETECTOR and high throughput of light). Again, the absorbance of the solvent is the reference cell is compared to that of solvent plus sample in the sample cell. UV spectro photometers of good design can measure absorption differences of 0,01% with reasona ble accuracy. The search for sensitivity High pressure liquid chromatography sys tems range in cost between $5,000 and $20,000. The price varies depending on complexity, convenience, versatility, and performance. Sensitivity is one of the present limitations of HPLC instruments, particularly when com pared to gas chromatographs. For this reason, many other types of detectors are under in vestigation, including molecular fluorescence and flame ionization units. One can also imagine that infrared spectrophotometers and atomic absorption instruments (for metal ligands) could be used. Another approach is the automatic addition of a color-forming reagent to the eluted sample in order to enhance its detectability. This is done in amino acid analyzers. Despite its enormous promise, high pressure 1 1. ANISALDEHYDE Z 3-ETHOXY-4.HYDROXY BENZALDEHYDE (ETHYL VANILLIN) 3. 4-HYDROXY 3 METHOXY BENZALDEHYDE (METHYL VANILLIN) 4 r-HYDROXY BENZOIC ACID MINUTES ISOCRATIC 10% CHCI3 GRADIENT elution benefits are shown at right in separation of food flavoring comjjounds. With isocratic (unchanging) solvent mixture at left, it is not possible to get a peak for component No. 4, benzoic acid. With a gradient, all four components are elided and clearly separated. 4" kj L_ 'Wo GRADIENT ISO-OCTANE TO CHCI3 CC 1718 highspeed liquid chromatography is the method of choice. In the production of polymers, highpressure molecular exclusion is used as the means to tell when the process should be stopped (conventional gel permea tion is too slow). A similar method determines residual monomers in polymers. Pharmaceutical houses use high pressure liquid chromatography for the determination of the presence and concentration of benzodiazopenes (tranquilizers) in tablets, thenothia/.iue (tough suppressant) in cough medicine, and for the measurement of de composition products in quality control of stored pharmaceuticals. Biochemical laboratories use it for the rapid isolation of viruses (interestingly enough, purely by size) such as Markoffs virus in chicken plasma. HPLC also is proving valuable for the analysis of dyestuffs and in termediates, which cannot generally be vaporized for use with gas chromatography. Also, it is possible, though not yet proved, to make the generalization that modern high pressure liquid chromatographs can repeat and improve any analysis now performed by ON paper or thin layer chromatography. One can visualize the flat sheet used in the latter techniques being rolled up and instated in a column, with an obvious gain in temper,ifnrcw control and isolation from the atmosphere.u Speed, separation, and repeatability are allQ /JL 1071,ne^nti Dccctneu tnur mintm-d, and then.' i, a fuitluT j"J,]n'lit in lllal til;- columns mu u-uscublc. Moreover. it is (liliiL'ult i" quantitate the tv- sults iit simpler techniques, and such desires as scunners arc expensive and hard to use. Thus, if quantitative lesults are desired, modem liquid chromatographs can even have a cost advantage. Don't dissolve the substrate To select the conditions for an IIPLC analysis, there are a few obvious basic condi tions. If a refracthe index detector is used, the solvent should--as far as possible--have a substantially different index ot refraction from the sample components of interest. For work with a UV detector, the solvent should have relatively low absoibaiice in the ultras inlet region. For obvious reasons, the stationary phase, or substrate, should not be readily soluble in the solvent. To keep the solvent from dissolving the substrate, one is generally chosen to be a highly polar liquid, while the other has very low polarity. Commonly, the substrate is polar and the solvent is not. If it is the solvent that is polar, the technique is known as reverse-phase chromatography. Tables giving the polarities of different liquids, and hence their suita bility for use together, arc widely published -and usually also show refractive index and UV transparency. An opportunity to increase the power of high pressure liquid chromatography, at the cost of complicating the instrumentation, is known as "gradient elution." Veteran gas chromatographers will recognize this as the liquid chromatographic equivalent of column temperature programing. With gradient elution, an analysis starts out with Solvent A which, during the analysis, is gradually changed in a timed and predictable manner to Solvent B. When gradient elution is properly used, it is possible to separate peaks which could not be separated with a single solvent or solvent mixture. It also is possible to speed up the analysis for sample components which are not very soluble in Solvent A, and to sharpen some of the later peaks, thereby increasing sensitivity. Gradient elution requires a second pump, as well as a solvent mixing chamber. Obviously, if a gradient consisting of two solvents is good, a gradient of three solvents is better, but fortunately, so far, only a few appear to have carried this bright idea into practice. R search into practice Up to now, the overwhelming majority of users of high pressure liquid chromatographs arc in government, industry, and university research laboratories. Because of the variety of Solvent SOLVENT POLARITY SCALE Viscosity E (AI 0 ) (cP, 20 ) Rl Fluorclkanes -0.25 n-Pentane 0.00 Hexane 0.00 Isooctnne 0.01 Petroleum ether 0.01 Cyclohexane 0.04 Carbon Tetrachloride 0.18 Butyl chloride 0,25 i-Propyl ether 0.23 i-Prooyl chloride 0.29 Benzene 0.32 Ethyl ether 0.33 Chloroform 0.40 Methylene chloride 0.42 Tetrahydrofuran 0.45 Methylethyiketone 0.51 Acetone 0.56 Acetonitrile 0.E5 i-propanol, n-propanol 0.82 Ethanol 0.B3 Methanol 0.95 Acetic acid Large Water Larger 0.23 0.33 0.3 0.3 1,00 0.97 0.47 0.37 0.33 0.65 0.23 0.57 0.44 0.35 0.3 0.32 0.37 2.3 1.20 0.60 1.26 1,25 1.358 1.375 1.404 1.427 1.466 1.438 1.368 1.378 1.501 1.353 1.443 1.424 1.403 1.381 1.339 1.344 1.38 1.331 1.329 1.372 1.333 UV Cutoff (mu) 210 210 210 210 210 255 220 220 225 280 220 245 245 220 330 330 210 210 210 210 ... 190 opportunities that high pressure liquid PROPERTIES chromatography offers, it is at least possible of some commercial solvents. Left hand that any analytical problem, no matter how numbers represent intractable, can be solved by the choice of the polarity measured proper column, substrate, and solvent. More by interaction with aluminum oxide. over, again because of the complexities among R1 is refractive which one can wander, almost any work that index. UV cutoff is done probably is publishable. represents the wavelength above which Increasingly, however, useful general the solvent methods are emerging. As may be expected, is transparent. instrument manufacturers are falling upon these with delight, and giving them the widest possible circulation. As a result high pressure liquid chro matography now is at the beginning of a period of explosive growth. As routine analytical methods become increasingly available, high pressure liquid chromatographs will take their places beside gas chromatographs in almost every type of analytical laboratory. O For abstracts of related articles from ARAC, NASA Regional Development Center, circle 678 on the reader sen-ice card. THE AUTHORS Zone L. Bitterfield is a chemistry graduate of Temple University and has experience at Drew Chemical and Wilson Pharmaceutical. His areas are quality control, lipids, and GC. Now he is working at Perkin-Elmcr with Herbert L. Kahn in HPLC. Kahn appeared in I R in February as product manager for spedrosccqiy. He has since moved to HPLC to be "where the action is." Zaiw, at left, is showing Herb where the sample goes in. OCC 1720 INDUSTRIAL RESEARCH--JUNE 1973 35 / ir J H iri \ QUALITY CONTROL 300 years ago was the scrutinizing eye of the alchemist. From the Fisher Scientific Co. collection, interpreted by I*R staff artist. i , k / \ Patrick W. Byrnes product manager Fisher Scientific Co. How chromatography meets the demands aqueous ammonium carbonate solutions. for many industrial quality control ap Lengthy wet chemistry procedures including plications is a story as diverse as industryfinal titrations are necessary to report these itself. Rather than attempt to cover the entire compounds to the nearest 0,5% or better. - subject, this article will suggest some rules of Analysis time per sample exceeds 100 min. thumb for the practical chemist to follow in By employing the correct column stationary assessing the applicability of gas chroma tography to his quality control problems. Ex phase and GC inlet system, the gas chroma tographic determination of these components, amples of procedures used in industry will be including data interpretation, requires less cited as further illustration of current than 8 minutes per sample. In this applica techniques. tion, the gas chromatograph is set up with a Gas chromatography is accurate, precise, thermal conductivity detector, tube pyrolyser and rapid. With the advent of digital in inlet system, and 7 ft (2.13 m) x % in. tegrators and computerized data reduction, diameter stainless steel column packed with interpretation and quantitation of results has Porapak or equivalent stationary phase. been simplified. The introduction of automatic The column is operated isothermally at 85 sampling devices has permitted automation of C with a helium carrier gas flow rate of about many GC procedures. Hence, GC can replace 40 ml/min. The detector is maintained at 150 lengthy or cumbersome bench chemistry C to prevent any sample vapors from con methods. densing while being detected. Sampling is The problems of industrial quality control done by transferring exactly 5 /d of solution are numerous and varied. However a flexible into a small steel boat which is placed in GC instrument and an analyst with basic side the pyrolyser tube and sealed. While knowledge of GC technique can adapt carrier gas is sweeping through the pyrolyser procedures to solve almost any problem. tube into the packed column, the tube is Consider the typical problem of accurately heated rapidly to 1000 C. determining the NIT and CO^ levels in Under these conditions, the ammonium OCC 1721 40 INDUSTRIAL RESEARCH--JUNE 1973 I 4 duetiutx ileteiq. n\ which wd] <;iu> a 'rvpeir.e If) ,t'iy f\ni- of comnomirl o mo^f- nvhil Ik'vo, There arc many similar analytical quality control .situations in the imnganic clu mical industry that can he more easily handled by gas ehroinatogiaphy than by current wet : / techniques. At the Chemical Manufacturing Division of Fisher Scientific Co., quality' control chemists l rely on GC for various quality control determinations. Fisher's 991? mole pure sol vents arc assayed by GC using either thermal conductivity or flame ionization detectors. The determination involves comparison of peak areas obtained from lot samples to those of standards having known mole purity. The following solvents are routinely assayed: \t acetone n,n dimethyl fonnamide acetonitrile 1, 4 dioxanc analine ethyl acetate benzene n hexane n-butanol iso octane isobutanol methanol chloroform carbon tetrachloride toluene methylene chloride -La- 2 propanol In some cases, GC is used to determine the level of certain impurities. In production of 1 1 carbonate stoichiometrically decomposes to NH3, CCh, and IhO. These gases are swept out of the pyrolyser boat into the column where they are separated and detected separately, A digital integrator automatically determines the peak areas. These areas are compared to areas produced by standard samples for quantitation using this equation: Area of std. _Cone, of std. - Area of unknown Cone, of unknown In this case, use of gas chromatography reduced analysis time from 100 min to less than 8 min while maintaining the integrity of the results. More important, proper control of __high volume production facilities was made possible by fast reaction to results that were beyond specification. Employing GC allows corrections or alterations to be made in the production process without waiting 1.5 hours to find the product lot unacceptable. A noteworthy point about this example is that the sample is an aqueous, inorganic salt solution--not normally thought of as subject to GC determination. The use of a pyrolysis in let device permitted relatively easy and straight-forward GC work. A thermal con- formic acid, for example, it sometimes is difficult to prevent build up of acetic acid. At Fisher, GC procedures for the determination of acetic acid impurity levels have replaced the old titration procedures. The GC pro cedure in this application offers three advantages. First, it is far less time-consuming and cumbersome, Second, it has specificity--it eliminates errors caused by other acidic materials present in smaller quantities. Where the titration would give total acidic im purities, GC quantitates the acetic acid in dividually and unmistakably as a single,' specific peak on the chromatogram. Third, GC's inherent sensitivity enables acetic acid detection at lower levels than previously possible by titration. Turned on by hydrocarbons A similar procedure is employed to deter mine the level of extractable organic sub stances in hydrochloric acid. The HC1 is extracted with a suitable pure solvent and the extract is partially evaporated. The remainder occis examined on a GC column and the separated hydrocarbon impurities detected by 41INDUSTRIAL RESEARCH--JUNE 1373 I O e-v> + j--n * a i j iOLLCi Oi I V* uCiiii "* f fr** jjon ilo GAS CHROMATOGRAPHY is simply a method for separating mixtures into their individual components, As with other chromatographic techniques, the sample is placed in a mobiie phase and carried across the surface of some stationary phase. The stationary phase is selected to in teract more strongly with some compon ents of the mixture than others and con sequently retard their travel. This inter action, based on a difference of boiling point, electronegativity, solubility, molec ular structure, and other factors, causes the various components to pass through the stationary phase at different rates and thus effectively separates them. Gas chromatography, keeping to its name, employs a gas as the mobile phase. Samples are first converted into the vapor state. Next, they are swept by a constantly flowing carrier gas stream through a long narrow column which is packed tightly with the desired station ary phase. A gas chromatography system consists of several basic components joined to gether to; B provide a constant flow of carrier gas. B permit introduction of sample va pors into the flowing gas stream. B contain the appropriate length of narrow bore, packed column. n maintain the column at a constant temperature sufficient to keep all samples in the vapor state. B detect the components as they elute from the column and provide a readable signal proportional in size to the amount of component. Vi Detecting devices can be universal like the Thermal Conductivity Detector, or specific such as the Flame Ionization and Electron Capture Detectors. The signal, or chromatogram, consists of a series of peaks, one for each com ponent. The peak retention time, or time required for elution of the component, is used for qualitative identification of the component. The peak area is used as a relative measure of the amount of the component. Utilizing appropriate quantitative standards, the chrcmatographer can obtain precise and accurate quantitative data. Gas chromatography is applicable to any substance which can undergo con version to a stable, nonreactive vapor and then pass through a column. A vast array of organic materials as well as the fixed gases lend themselves to GC determination. Most inorganic compon ents are not amenable to GC work since they resist conversion to a stable, non-reactive vapor. Some inorganic sul fates and nitrates, by contrast, will con vert to stable fixed gases, and hence enable GC determination, providing an indirect analysis. y a highly sensitive flame ionization detector (FID). The FID responds only to hydrocar bons and a well-designed FID will detect levels as low as 50 ppb. . In addition to being highly sensitive to hy drocarbons the FID does not respond to water. In some instances, where the hydrocar bons are moderately soluble in water, direct water injection eliminates the need for ex pruoursts of ammonium carbonate is an excellent traction. Even a considerable amount of water produces little or no response with the FID and, as a result, there is no interference with example of how GC even small hydrocarbon peaks. saves time, reducing Perhaps the most predominant use of gas a 100-nun operation to less than 8 min. chromatography at the Fisher Chemical Division is for quality control of pestieide-free solvents. Following a procedure outlined by the Food and Drug Administration, samples from each lot of each solvent are analyzed by gas chromatography coupled with an electron capture detector--the most sensitive method used today for detecting and determining halogenatcd pesticide residues. The detector sensitivity is adjusted so that 1 nanogram (10~9gram) of heptachlor epoxide (chosen as an average standard by the FDA) per milliliter of solvent makes a half-scale deflection (50-division peak) on the chromatogram. To meet Fisher specifications, no solvent can contain existing impurities that produce a deflection of 1 mm on the chart. This means the impurities must be less than one part (heptachlor epoxide) in 50-billion parts. The solvents assayed in this manner include; acetone acetonitrile hexane methanol benzene ethyl acetate methylene chloride carbon tetrachloride 1-2-diehIorothane n-pentane petroleum ether 2-propaiiol occ 1?23 INDUSTRIAL RESEARCH--JUNE 1373 ||,i-,i` ((' il I !M i n( i Hi 11 nth -i 14 `il CO I,, I ,I i wim i ilheii.iU M'l'i'.i ill t' n - i.llirua iov selecting GC n\; r Mime i.llu i technique: S3 CC UUihuds sau1 tunc. (3 GC procedures air moie sensitive, a cc is moie specific, a CC procedures air simple and rarely cumbersome. When try inq lo decide between CC and bench chcmistrv procedures, weigh the benefits listed ulnae against the initial capital outlay ior the equipment. Gas chroma tographic systems enpubie of a wide range of qualitv control sunk can he obtained for less than the cost of a technician for one war. Chromatographic variety There is certainly no shortage of gas chromatographs ior the user to consider to day. A wide selection of systems offering vary ing degrees of capability with one, two, and four columns, a choice of detectors, and other components, plus all the sophistication and complexity one could want, are on the market-each with its appropriate price. Since most GC procedures require the capabilities of a dual column unit, discussion here will focus on these systems. There are, however, simpler procedures which can be carried out on a single column instalment, but that's another subject. What then arc the features and performance qualities that a gas chromatograph should base lo represent a good value for the analyst in quality control? Stability ranks as the most important single characteristic in selecting a gas chroma tograph for quality control work. Good stability means repeatable retention time (or elution time) and this gives the analyst con fident peak identification and precise results. Retention time, in turn, is grossly alfected by temperature and flow fluctuations. The highly stable GC instrument of choice, therefore, should employ a differential flow controller for control of carrier gas to each column and should offer temperature stability of about 0.5 C. _ - Most GC systems now available utilize state-of-the-art detectors and have adequate sensitivity to detect levels normally sought in quality control. A typical flame ionization detector, for example, will routinely detect less than 1 ppm of most hydrocarbons. The second-most-important characteristic is reliability. The instrument must deliver consistent results around the clock. Instrument failure can delay an entire production facility and often can eliminate the only means of assaying product quality. Since down time is an inevitable occurence, however, the in strument should be easy to troubleshoot and repair. Before selecting a GC instrument consider the following questions to help minimize down lime hefoie it occurs. Is the instrument t* ^ <v a, J J ir V3 .3 modular? Does it employ state-of-the-art INEXPENSIVE solid-state electronics? Who services the warranty, and what is their reputation? Several gas chromatograph manufacturers have recognized the potential of GC in indus gas chromatograph in use here it typical of units designed for quality control work. Its dual column trial quality control and have developed in system will accept struments specifically to suit quality control a variety of needs, A recently-introduced gas chroma tograph has a versatile dual column system sophisticated components. which features . multidetcctor capability, These include: dual flame ionization detector with standard dual channel electrometer; electron capture detector, supplied with an ECD Linearizer (displays linear response to concentration ranges of 2 x 10*); and dual thermal conductivity detector, filament or thermistor type. This choice of detectors combined with a large column oven introduces dozens of ap plications possibilities that were previously unavailable with an inexpensive GC system. THE AUTHOR Chromatographers can, for example, employ Patrick H', Byrnes is two dual detectors simultaneously enabling gas chromatography product manager split effluent display (FID, ECD), or for the Analytical simultaneous TCD, FID operations, plus Instrument Div., additional other operations. Fisher Scientific Co. Such a unit offers the temperature and flow stability needed for precise quality control He previously managed their applications laboratory, and is work. In addition, the choice of temperature a specialist programming provides the chromatographer in developing with all the versatility needed to accommo GC procedures. date analysts in almost any industry--chemi cals to textiles. This economical instrument in the $3,000 price range, makes available a 4 cn AT i **-'" quality instrument capable of adapting to numerous QC procedures, including pyrolysis. r^t * - - r,; i- With instruments of similar description and price coming on the scene, the quality con trol chemist can upgrade many of his current bench procedures; often reduce production costs; and always save analysis time. D \ i For abstracts of related articles from ABAC, NASA Regional Development Center, circle number 07G on the reader service card. ^-OCC 1724 INDUSTRIAL RESEARCH--JUNE mi et me start by saying that this message equipment" as an isolated incident. Usually, Lis not being beamed out to the fat cats these days, a need indicates the purchase of who have a fully-equipped lab and/or theequipment and if the proper tools are selected capital equipment budget with elbow room to (and used properly) the needs will be ful spare. Actually, this really is a moot point, filled in a reasonable amount of time and -- for I suspect that all the fat cats died with the everyone will come out ahead. There should mid 1960s. be and is less of the "emotional" purchasing No longer can a laboratory justify the pur which usually spelled trouble for the lab user, chase of a "toy" which is fun to pliy with but the instrument manufacturer, and ultimately does not justify its own existence on a month- for the management which okayed the original to-montb basis. It has been observed that purchase. Dennis R. Gere t^1*s mec^iaidsni *s not unique to the tools of manager separation laboratory, but applies as well to project sciences planning and even to the chemists themselves. Varian Associates Today, then, we have a much more sophisti Instrumentation or classical analysis? Let us examine, then, some representative approaches used to reach a sensible decision cated and discriminating group of people pur for purchase of chromatography instrumenta chasing and justifying the purchase of labora tion. To begin with, do you really need tory equipment. instrumentation? This trend towards a tougher management This cannot be answered for all cases in line on purchase of equipment is even more evident and significant in the smaller labora tories where funds are limited and competi general, but rather each case to be measured on its own merits. What one usually pur chases these days in terms of chromatography tion for use of the funds is severe. What does equipment is not just a piece of hardware, but a person in such a laboratory do if lie is contemplating purchase of chromatography equipment? rather a "capability." This is often a com plex and expensive capability and dicrefore requires some thought and effoil to make suie First of all, rarely does one simply "con the "capability provided" is well match-, d \\ ith template the purchase of cinematography the "capability needed." --. __ _ OCC 1725 INDUSTRIAL RESEARCH--JUNE 1973 Modern high-performance liquid chroma tography, (HFLC) as used in tin- |.harmaceutical industry provides several convincing arguments in favor of chromatography in strumentation over such wet chemical tech niques as thin-layer chromatography (TLC). For a tv pical analysis, a total of six man-hours would be allotted to the TLC technique whereas a total of one man-hour is all that is required for the ITPLC technique includ ing pre-column work-up and post-separation data reduction. Not only does one save time--but also new dimensions of resolution, precision, and ac curacy are now attainable. The same is true in the comparison of the gas chromatography of 17-ketosleroids in pregnancy urines. What are the choices? So, you're convinced that the added speed, sensitivity, through-put, and resolution justify the capital expenditure to expand the capa bility of your limited budget lab. You now begin to explore the many pathways that could lead you to having such devices in your facility. If you simply walk in to your man agement and quote them typical prices "coldturkey" for a fully loaded chromatograph, you can almost be assured they'll send you back to seek lower cost alternatives. Perhaps they will suggest that you pur a good l)uv from the standpoint of rrh.ib'.'itv and quality, 'nit from an absolute dollar standpoint it will cost 35 to 957 of its original selling price. A well-designed, useful chromatograph should have no trouble lasting at least ten years. That means that a laboratory' rarely will give up one of these devices short of some disaster. If they do, it's because they want or need a more capable device (how does your chemical problem compare with theirs?), or because they have had a lot of downtime with it. The best possibility you have of obtaining a bargain is visiting a laboratory which is being closed down. These days there are, admittedly, quite a number of these happen ings. Even then, the good capital equipment is reallocated to the other parts of the com pany before the outside public is allowed to look over the used equipment. Assuming that you can find a used piece of equipment (a used high-performance liquid, chromatograph is impossible to find at this time), check carefully into a couple of other factors before you purchase it. O Is the unit operational at this point? Will the seller aid you in making sure it is operational? Is the unit amenable to servicing? Are the replacement parts readily avail- P f,-k^- -- ------- chase a used model. Unless you are very lucky, that pathway is rarely worth pursuing. Used chromatographs are a tough commodity to find. It's something like buying and selling a used car. You must keep in mind there are several different terms used in describing the value: actual cash value, wholesale sell ing price, and retail buying price. Whereas your management expects you to find the model to match your needs at per haps 302 of the new price and only slightly used, you'll find a seven-year-old model sell ing at 70% of its full price and, upon close scrutiny, it doesn't have your solid-state electrometer which is now considered stand ard equipment and the temperature programer is a first generation design. There's even the problem of locating a used device that will meet your needs. The instru ment manufacturers rarely offer used equip ment, for a variety of reasons. Used equip ment usually means a demonstration device used in an application lab for no more than one year, Usually, it is fully reworked in the factory before being shipped out, and then leaves with a new device warranty. This usually is able today? Beware of the model whose manufacturer has ceased operation! Leasing is for tax saving Perhaps your next option would be to try and lease some equipment to avoid the capital outlay for the whole item at one time. This option rarely turns out to be of any value in easing the original justification for obtaining the equipment. Its biggest value is as a tax writeoff benefit. If your management is unwilling to lay out the original purchase price at this point, the idea of signing up for 36 monthly lease pay-. ments without any gain in equity doesn't appeal to them either. (No, Virginia, there is no 6-months lease, where you can send it back if you don't like it at the end of the short term!) If yours is a small independent laboratory, at this point of desperation you might con sider going to a private bank to see what they will do for you. Usually this is a very discouraging ordeal. Bankers take a very conservative stance concerning scientific equipment. This means you must have 502 of the purchase price available in assests OCC 1726 INDUSTRIAL RESEARCH--JUNE 1973 C33 K-j:. t'Tf'n.'j form <>ri qr-jUti oi on I30'jr>' r' 1 n !v' i'O'/'d .T`y , ..Mvlv v-.H' 'J. 5 Cliro^ fMrrj;Ay Hie cpuU'iit j i <;f kri < * rou-k tn 't.irc . furiiv:,* d by cr'-'ri:,'. .* In-, .i.-di'jd ^ .pry oCt-.j;.1 ti.j Siiico LMtty oi ' > i$ off imr'c t.^r t!ie k ,/;-v * '; : o c.. ^i.UKO- gram shows the thretJ c.unmon 17 k :tostefOiris m urine, nn:dy;5rj as T.\"3 .-krw.itiv^s, as .,t-1i as pregnancdiol. The tntdrrq! starvutrd >s chnkjsfprol. j | 1 1 1, Pre^'iw^cdfnl (TTvI^I 2. Ah'irc ^tron<5 U ivlb) 3 Etiotliv-'lacolon^ (TiV.S) 4, D<-'!svc>o.piao(ircstPfuMO (TM$) 5. Choi-^p.ol (TiMS) (interrKil vtand.ird} 2 0 5 10 15 20 *im Conditions: flame fonsmtion detector; 6' x 1/4" glass column with 1.5 i OV-17 on 100/120 HR Chromosorh G: 200C; N2 at 30 tnl/min. and the 50% you borrow should be paid back in no more than three years at stiff interest rates. Well, you're back to your own return on your assets calculation! Oftentimes the next idea you have con cerns buying components and putting them together yourself on a bare-bones allocation. The red flag really goes up here concerning man-power availability and hourly labor costs. You must make sure you are buying the state-of-the-art components first of all. Sec ondly, you need someone available in your facility who can lash it all together and make it work, and service it when it is down. A survey of a couple of the larger pharma ceutical firms which opted for this type of entree into high performance liquid chroma tography indicates that this is not the best way fur a fiscv.ib-lvsponsibli' m ^.lniz.it'.'.ja to go. \oil'll find attiT a couple ut ye.ut!i it the people you assigned to assemble and inn the equipment have learned a lot alvmt the technique, but meanwhile vour competi tors have turned out four times the analysis workload on equipment which was purchased with a systems responsibility (by the manu facturer ). Remember the commercial equipment is designed not only for ease of operation, but also very importantly, it is designed for serv iceability. Spending some time comparing mean-time-to-failure and mcan-down-time of commercial system vs. put-togethcr com ponents can be very revealing. Make the salesman work Finally, then, we come squarely back to the need for a systems responsibility. Justify your purchase on real need in your labora tory coupled with a capability which you don't possess at this time (or perhaps in not sufficient quantity). You should be talking to a salesman in the early stages where he can help you define your needs in terms your management can easily recognize. He will also be helpful in referring you to current users of his equipment, com petitor equipment, and even basic-component equipment. He can also put you in touch with other members of his own team (just who else is on his team and why?). He'll let you talk to his development engi neers and scientists who can tell you not only why a certain feature is available, but how a potential new feature could be added when the state-of-the-art advances. Concern ing features of equipment, don't forget that the professional salesman can help you relate a hardware feature to a real benefit for you, the end-user, on your chemical problem. He also has access to an applications labora tory--a benefit which usually becomes ap parent after the sale, during the critical startup period of new equipment. Remember, it's not always fruitful to simply send in a customer sample to the applica tions laboratory and base your buying de- XUTOM4TION can come in various degrees. Defending on your needs, the more automation you hate, the lower are your costs. Cost savings based on sample throughput Item Manual Operator Costs* Integrator Instrument supervision Area measurement Composition calculation Report writing Total/sample S .50 3.00 1.67 1.00 $6.17 $ .10 .30 1.67 1.00 $3.17 `Based on 10 pj&ks, 10-minute chromatograms, $10/hour/operator Sjvinas/yeor Sampl?s/day X savmgs/day X work days/year Payout/year - -------------------- _!-------------------------- - ------------------------ System cost System cost Computer $ .00 .30 .05 .05 $ .45 OCC 1727 54 INDUSTRIAL RESEARCH--JUNE 1973 cision on the "beauty" of the chromatogram which it returns to you. Better that you ar range a visit to one of these laboratories and observe the equipment in action. Even better, get your own hands (or those of one of your laboratory personnel) on the equipment in the applications lab and operate if yourself. Keep in mind, also, that the applications staff probably will be available to you for consultation after the sale, a very useful service. They can provide you with a con tinuing source of technical data on the care, feeding, and expanded use of your equip ment, Oftentimes this can be in the form of short courses, basic how-to manuals, and continuing bibliographies. There is also another group on the sales man's team that can be of vital assistance, the service engineers. At some time or other all equipment will develop a problem. The abilities of the service crew can substantially affect your minimum-down-time and frus tration level. This capability can rapidly overcome the difference in original purchase price of a complete commercial system vs. the put-together-yourself component kit. But there is one kind of do-it-yourself that can make sense, A good compromise in the approach of putting components together yourself is to purchase a chromatograph which is designed in a modular concept. Finally, don't fail to consider automating features of a chromatograph. It may seem in compatible to consider an automated chro matograph when funds are limited. However, if a heavy workload is anticipated, automatic sample introduction and automated data han dling can, in fact, pay for themselves. Oper ating expenses are reduced by the manpower savings resulting from one or more of the following areas: instrument supervision and maintenance, quantitative calculations, and report preparation. Faster sample through-put THE AUTHOR Dennis R. Gere has worked six years makes it possible to reduce the number of for Varian Associates, chromatographs required for a given work most recently as manager of separation load. sciences in the Let your needs dictate your purchase applications lab. requirements. Justify these needs as credibly This month he is newly employed as you can define them. Seek assistance in at Hewlett-Packard's defining these needs and requirements from Avondale Div. the instrument salesman and his team of experts. Avoid the pitfalls of buying for emotional reasons or on strictly price con siderations. t Determine how your chromatograph can and will do the work for you. Despite what some bankers might think, there are few * 1 investments that pay back better or more dynamically than can a well designed chro matograph. For abstracts of related articles from ARAC, NASA Regional Development Center, circle number G77 on the reader service card. ee~t72r INDUSTRIAL RESEARCH--JUNE 1973 55 \ 'V o \ fV -w f \ \ *\ \\ f: f *,, \ \ -- 'i Accurate repeatability from 01 jj] to 50 ml If you need to measure or deliver precise samples ... we have the world's largest line of dispensing devices from which you can choose. Our 700 Microliter syringes grew up with the GC industry ,,. and have become the standard measuring devices in laboratories throughout the world. Our 7000's contain the full volume in the needle. Our 1000's have a Teflon* tip for leak-tight seals for gases or liquids. And our new Sub-Microliter Liquid Injector is a tapered capillary needle with high repeatability in 0,1 /Jtl volumes, n if you need to deliver samples anywhere from 0.1 /il to 50 ml, we have just the syringe for you. Our syringes are described in our catalog ... let us send you a copy. Write to Hamilton Company, Post Office Box 7500, Reno, Nevada 89b02. DuPont registered Uademark Vl, \ x \.\ X \ V /T / -V r\* \ \\ \ \\ \ X *v V \ \ V \ \ Lr 1DIAL FOR DATA (IreoV 600/621-0560 - ->i*irv card 06C 1729 B. P. Goodrich Chemical Company g i v 13 i o * o* roc a r, i o i M > t i c o r a r 8100 OAK TREE IGULEVARO ' CLEVELAND, OHIO 44131 PHONE 218-53 4-0 2 0 0 JOHN L. NELSON December 5, 1975 Mr. Raymond Abramowitz Hooker Chemical Corporation River Road Burlington, New Jersey 08016 Dear Ray: Enclosed is a copy of a report "Progress in Vinyl Chloride Containment", which was distributed yesterday in a media briefing in New York. As a member of the Vinyl Chloride/Polyvinyl Chloride Producers Consnittee of SPI, you may be interested in some of the things B.F.Goodrich has done in meeting the challenge of the vinyl chloride health problem. Yours very truly. J.L.Nelson/ja t V { i * * ' OCC 1730