A close Jook at thepill and other molecules .. With effective instruments Pandora’s ° Pill Box The Art of Making Fine Chemicals At the 1965 Pittsburgh Conference, Hewlett-Packard introduced to the chemical industry a large-scale preparative gas chromatograph. Where prep GC had previously been limited to producing,at best, a few milliliters of high-purity chemicals during.a long day’s operation, this new H-P instrument easily separated a liter of equally pure materials in a few hours. Asis often the case with technological advancements that suggest a commercial value, incredulity ensued—partly because claims about the instrument were misunderstood, partly because the largest element of the scientific community is from Missouri. Largescale prep GC became one of 1965’s chemical controversies. Yet today, a scant 3 years later, H-P’s large-scale prep GC is a fixture. in scores of chemical companies around the world, on the basis of its demonstrated rather than claimed capabilities. The characteristic elements of the H-P instrument are the 4-inch diameter column whose relative capacity ratio is more than 100 times greater than conventional prep columns; and the flow homogenizer, an ingenious piece of hardware that removed the last barrier to the use of such large columns, i.e., non-uniform car- rier gas flow leading to loss of resolution. Because of these two elements, the instrument has a gargantuan appetite for performing high-purity separations. For example, it separated a gallon of rectified turpentine (that’s almost 4 liters) into 1733 milliliters of a-pinene, 701 milliliters of S-pinene, both with a purity of over 98%; instrument running time was 30 hours. In a 7-hour run, the instrument separated 970 milliliters of Cs, Co and Cio methyl esters, collecting 906 milliliters in the following purities: Ce and. Cio, 99.8%; Co, 99.2%. The same work would have taken 6 months on a conventional prep GC. ’ Based on these and many similar separations, the importance to the chemist of the H-P prep GC is easily described: it produces high-purity chemicals so fast, so conveniently, and so economically that every chemist who needs them—analytical, organic, biomedi- cal—can now prepare his own, whether he needs a microliter or several liters of a pure substance . . . for use in reaction studies, for analysis, or even for commercial purposes. Of course if all three types of chemists work in the same lab, the H-P prep GC also creates a new problem: whogets to use it first. For help in solving most prep GC problems except this one, write for Data Sheet 775/6. Although five to seven million American women have already consumed more than four billion oral contraceptives, there is still much uncertainty concerning their long-term effect on the human body. Theissues are scientific and the questions involve chemistry, biochemistry and physiology ... endocrinology, pharmacology, and gynecology. The answers are in widespreadresearch in every scientific discipline concerned. It is in the chemical and biochemical disciplines that HewlettPackard assumes its concern with the massive anti-fertility drug research program, specifically, through its Gas Chromatography Applications Laboratory, in Avondale, Pa, Thus far, Avondale’s involvement has centered around two of the most widely used synthetic hormones: Norethindrone and Mestranol. Both are labile steroids, subject to thermal degradation. When these steroids break down—whether during manufacture, in the human environment, or during analysis—they form a keto analog so similar in chemical Structure to the original molecule that it is extremely difficult to differentiate one from the other. The rub is that the scientist mist be able to tell them apart since the steroid is an effective antifertility agent while the keto analog is not. Thus there can be no confidence in any chemical analysis of the pill unless it is first demonstrated that the analytical procedure can separate the steroid from its keto analog ... and that it can preserve the chemical integrity of the two types of molecules during the analysis. As far back as 1964, our application chemists proved that KETO the Model 402 High-Efficiency (b) Gas Chromatograph has both capabilities. The proof is pre3 sented here in the form of three chromatograms. The first, an KETO @@ analysis of a sample containing the two steroids, shows the presence of Norethindrone (b) and Mestranol (a), and the ab(a) 2 sence of their keto analogs: this \(b) is proof that the 402 respects I the chemical integrity of the steroids. If the Model 402 were causing degradation of the steroids, the chromatogram would show the presence of at least some quantity of the keto analogs. The second chromatogram shows the presence of both the steroid Mestranol and its keto analog, thus demonstrating the 402’s ability to separate one from the other when the two coexist in a sample. The sameis true of the third chromatogram, this time with respect to Norethindrone. Lest it become obscure at this point, the noteworthiness of these analyses is twofold: they demonstrate the 402's ability to detect the labile steroids used in anti-fertility drugs without causing degradation during the analytical procedure; and its ability to separate compoundpairs of such steroids one from the other and from their keto analogs. Extrapolating from these points, the 402 can be seen as a fast means for quality control in anti-fertility drug preparation, as the basis for investigation of its clinical progress and beyond that as a possible means for in vivo patient monitoring. A report of the anti-fertility drug analysis as it was originally presented in Facts & Methods, Vol. 5 No. 3, is available on request,