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// // ... // / : >\ V . / ft \ ) ub Food and Drug Administrn- Tlion is one of the largest employers eluding the colorful Harvey Wash ington Wiley, who trained as a of analytical chemists in the United medical doctor but switched to n States: about 400 in the field career in science. Wiley left his laboratories and another 2*>0 in the teaching duties at Purdue Uni Washington headquarters. The versity in 18S3 to become Chief agency has moved n long way from Chemist of the U.S. Department of the days when the chief laboratory Agriculture. Starting with two or instruments were the analytical three chemists \vhr*se primary duty balance and the microscope, and was to analyze fertilizers, Wilov the prime analytical challenge was soon expanded his activities to in the detection of tenured oil in olive clude studies of food adulteration. oil, The changes reflect not only At first he considered the main the development of analytical sci threat to be to the consumer's ence but also the transformation in pockctbook instead of his health. modem life. But as public opinion began to solidify in favor of a. national food Kvolutlon of on Afoncy and drug law, Wiley knew that to justify legislation, it would be es In the last quarter of the 19th sential to establish the degree of century, the United States under health hazard. Around the turn went a transition from a rural to of the century, he formed lua famous an urban society, and millions of "Poison Squad," a group of healthy citiacno who formerly produced young men who, under his direc their own foods, medicines, and tion, limited their food intake to a other consumer products now had to closely supervised diet to which depend on commercially processed known quantities of preservatives products. Although the majority and adulterants had been added. of commercial producers were legiti Their urine and feces were collected mate, others were not. It was not and examined, and a close chock unknown for a food processor to was kept on their state of health. make canned peas greener by adding It was a rough test, by today's copper sulfate, to preserve foods scientific standard*, but although with formaldehyde, borax, or so results were not entirely conclu dium benzoate, or to defraud the sive, it became evident that such consumer by adulterating expensive preservatives in foods were indeed natural products with cheap sub harmful to human health. stitutes. Tin* market abounded in After a long and often discourag quack drugs whose popularity owed ing st niggle in which he was opposed much to their considerable alcohol by many pressure groups, Harvey content. Wiley finally saw the Fond and In time public concern became Drug Act of lf)0C passed by both aroused, and a number of scientist* Houses of Congress end signed into began to attack the problem, in law. lie then found that the hard est part of the fight was ju i lo ginning: that enforcement, oi tin. law wua to be even more dillicult than its enactment. But us flu- opponents of food and drug p-tzulalion continued tlicit opposition to regulation, ho and his varum- suc cessors through the years main tained a record of equally vigorous enforcement. Originally, enforcement activities were lodged in the USDA Bureau o! Chemistry, but in 1927 the I-'o.id and Drug Administration was es tablished as u separate entity w it Inn USDA. After passage of the Bids Food, Drug and Cosmetic Act, containing such innovations us pre market testing of new drugs, I DA was removed from USDA mul placed under the Federal Security Agency, which became the nucleus of the Department of Health. Edu cation. and Welfare established in 1053. The basic stnutnre re mained much tho same until 1'J'J 1 when the first of several major re organizations was announecd. The present structure appears in f ig ure ). For many years FDA was a small agency with a tight budget. A.- recently os 195o, a staff of MX) with a budget of only So.l million was responsible for regulating g".iU with an annual value of ?nd billi- -n. After a survey and report by a Citi zens' Advisory Committee in I'.l.Vi I DA was in.-tructed to quit.I-tipu- its resources to carry out re sponsibilities more HTrrm rly Tin- picture for fiscal year 1972 w:i considerably different lion; il.:` ! 19.V>. FDA's budget w av Sill) 22 A ANALYTICAL CHEMISTRY, VOL. 44. NO. 13, NOVEMBER 1972 HONS 084098 REPORT FOB ANALYTICAL CHER/itSTS HELEN L. REYNOLDS, HYMAN R. EIDUSON. JOHN R. WEATHERWAX and DONALD D. DECHERT Food and Drug Administration, Washington, D.C., and Los Angelas, Calif. Since the establishment of the Food and Drug Administration, the problems to be solved and the tools to solve them have increased several orders of magnitude. At the same time, acceptable levels of sensitivity in measurements have decreased from the milligram to the nanogram or picogram level /*T\r\ rnnr Q million, nnd the agency had more than 4000 omployccs, although those amounts are still short of those needed to attain FDA's goals (J). FDA Today Resources for FDA's regulatory work must be spread over a wide area of domestic nnd imported products. In Addition to the basic FD&C Act, the Import Milk Act, the Filled Milk Act, and the Tea Importation Act, FDA is respon sible for enforcing the Food Addi tives and Color Additives Amend ments, tho Kefauvcr-Harris Drug Amendments, the Fair Packaging and Labeling Act, the Hazardous Substances Act* and its amend ments (Child Protection and Toy Safety* Acts and Poison Prevention Packaging Act), and portions of the Public Health Service Act in cluding the Radiation Control for Health and Safety Act. Besides its other regulatory work, the agency must test and certify every batch of color additives, antibiotics, and insulin drugs manufactured in the UJ5. The retail value of all prod ucts under FDA jurisdic tion is now over S230 billion, representing al most 38 cento of every dollar spent by consumers. The current annual cost of FDA protection of con sumers is about 53 cents per person. In contrast to many organiza tions, FDA's main arena of action is in the field. Many of the episodes that catapult FDA into the news begin ot one of the IV district offices located in major cities throughout tilt* *U.S. An inspector is sent to 'heck a complaint, received ut the district level, or he sees the first indications of trouble in a routine establishment inspection. He ob tains samples (usually by purchase) and sends them to the district office for laboratory examination by chemist8 or microbiologists. If the results warrant, the investigation then expands, sometimes to a fullscale program. If an imminent hazard to health is involved, several districts may cooperate in roundthe-clock work until tho problom has been brought under control. FDA may take action against a violation in one of several ways: by court-ordered seizure of the product, injunction, or criminal prosecution in a court of law. Each type of action must, of course, be based on sound evidence, and those who are accused of violation are protected by due process. The most serious type of action is the criminal court case; it is also the most expensive in terms of money, manpower, and time. Seizure is carried out by the district through the Federal courts, but the decision to prosecute must be made at head quarters in Washington. Since its earliest days, FDA has depended heavily on laboratory analyses. An analytical result can be no better than the method used to obtain it, and the search for bet ter methods is unrelenting. Even under the most severe regulator}* pressures, some time has always been reserved for methods develop ment. A regulatory method need not be elegant, but it must have certain other characteristics: It must be accurate, precise, reliable, specific, sensitive within the range of interest, and practical. Prefer ably, it will be rapid and inexpen sive, but these are secondary con siderations. Most important, it must be capable of giving the type of results that can be used success fully in court. The scientific wit- Figure 1. Organization of Food and Drug Administration (July 1972) ANALYTICAL CHEMISTRY, VOL. 44. NO. 13, NOVEMBER 1972 21 L Waport lof Analytical Chamliti Figure 2. Chemists t Kansas City District examine food samples for pesticide residues by gas chromatography ness for FDA must be able to de fend his testimony against cross examination by a defense attorney. The defense may bring in other scicntific experts who testify that they obtained different results by a dif ferent method. For these reasons, FDA prefers to use standardized, validated methods such as those of the United States Pharmacopeia (f) or the National Formulary (3) for drugs and the Association of Official Analytical Chemists (AOAC) for foods and other com modities U). "One-man methods'1 are open to attack and must be strongly supported by validation. FDA has been quick to adopt modern techniques and instruments as they arc developed and to ex ploit them for the agency's unique mission. The early reliance on color tests, volumetric and gravi metric analyses, and microscopic identifications has undergone com plete metamorphosis. FDA now utilises a range of techniques in cluding infrared, visible, and ultra violet spectrophotometry; nuclear magnetic resonance, atomic absorp tion, electron spin resonance, and mass spectrometry ; gas-liquid, thinlayer, liquid-liquid, partition, ionexchangc, and absorption chroma tography; X-ray diffraction, fluo rescence, electron microscopy, and polarography, among others (Figure 2). Mycotoxins Problems of regulating consumer products tire rarely single incidents llmt can be solved simply and quickly. Even the recent death from contaminated vichyssoi.se soup was only one tragic episode in the continuous fight against toxic orga nisms such as Cloalri<Jium b'olulin um. Many of FDA's most serious prob lems arise front natural contami nants. Modern analytical tech niques permit FDA to detect many chemical contaminants that pre viously escaped detection. An ex ample is the mycotoxins, of which the aflatoxins arc best known. The aflatoxins are a group of toxic metabolites formed chiefly from the mold Atpergillut flavut, which oc curs naturally on groundnuts and other crops. Aflatoxins have prob ably infested crops since the be ginning of agriculture but were not recognised as a health hazard until the early 1900's, when an outbreak of "Turkey X" disease in England was traced to animal feed containing peanut meal from moldy peanuts (5). The research laboratories in Washington undertook an extensive research program on all phases of the mycotoxins, including their na ture, effects, formation, natural occurrence, and assay. Techniques were developed for the isolation and purification of the mycotoxins for chemical characterization and identification (6'). A single nut was labeled radionctivoly to check the homogeneity of a groundnut com posite () Phvsicochemienl pro cedures were based on fluorescence and thin-layer chromatography and bioassiys first cm ducklings as test animals ami then more sitn-essfuliv on feratologjcnl effects it) the chicken embryo ($). Continuing research has disclosed a new myeutoxin, named aspertoxin, which has been isolated and its structure eluci dated ($). Specially trained district labora tory analysts determine nfhiroxmu in import and domestic samples. The New Orleans District lias been designated as a specialized labora tory for the analysis of mycotoxins in FDA surveys of various rla*cs of foods to establish their potential for mycotoxm contamination. Tin* sensitivity of the nflatoxin chemical assays is now well below *20 ppb. Methodology has been extended to a number of commodilie** ami to large-scale samples, in which a direct extraction of wnter-wetted samples with chloroform is com bined with a silica gel column for defatting and cleanup (JO) This procedure provides enough material for chemical confirmation, for ex ample, by formation of derivatives with thionyl chloride and formic or acetic acid (//). Mercury in Foods Heavy metals in foods--lend, arsenic, mercury, cadmium--have plagued mankind for generations, and as one source of contamination is brought under control, another seems to take its place. Mercury in fruits and vegetables as a result of agricultural practice* was a source of hazard during the early 1930's, but the development and acceptance of the "safe" organic pesticides were thought to solve the problem. But by 19.'>2 mercury had a sain becomc a matter for concern because of its use as a fungicide to treat seed wheat. Industrial use of mercury, chiefly in chlor-alknli plants, has now generated a greater hazard: The mercury enters aquatic sys tems and is transferred to the food chain through fish in the form of highly toxic methyl mercury. In late 1909 a family living m ar Almngordo, N.M., wn* poisoned after eating meat from laughmred hogs which had been fed mercurytreated seed grain (/;?). A colori metric method was already a\ailable to determine the im n ur\ eontent of the grain (Mr, although lengthy, it hud been (o||ab--r:in\* lv studied by the AOAC and a- suit able for the relatively mm.ill num bers of grain sample* that I0\ HONS 0 8 4 1 0 0 Hfport for Analytlcsl Chtmliti normally cheekrd during a year. The grain sample is digested with HNui utid HjtiUi under reflux in a itpecin! apparatus, interfering metals are removed, nod mercury is iso lated by dithiamie extract ion and then determined by photometric measurement nf mercury dithizo nate. By this method, analysis of the groin fed to the hogs showed 32 ppm mercury (/-?). The method proved to be unsuitable, however, when ilio need arose t-o determine mercury in fish. Japanese families suffered poison ing from eating fish contaminated with mercury in n number of epi sodes during the liKiO's in the area of Minnmntn Bav and again in 1904-415 (14) at Niigata. An early as 1904, Sweden became concerned about the contamination of its food supply with mercury arising from the use of mercurial fungicides in agriculture and mercurial slimicides in paper mills. In 1908 the Swedish delegate to the Codex Committee on Food Additives reported that mercury levels in fish had become a matter of real concern. In early 1970 Canadian authori ties became alarmed at the degreo of mercury pollution in certain Canadian lakes and rivers, owing chiefly to chlor-alk<iU chemical plants, and they closed them to commercial fishing. The FDA dis tricts at Detroit, Minneapolis, Cin cinnati, and Buffalo began an im mediate investigation of the Great Lakes area. Chlor-alkali plants were visited, and agricultural run off and other industrial sources of pollution were checked. Samples of fish from suspected waters were collected and analyzed. Data on mercury in fish were reported from n number of sources, many of them outside l'DA, and none of the sources vised the same analytical procedure. There was no means of judging the accuracy and reliability uf the data. To provide reliable data on which to make a sound regulatory decision, it was necessary to have a rapid, accurate, precise, sensitive analyti cal method which could be oollnborativelv studied and adopted as official bv the AOAC. The Denver District, which had already begun method studies, was asked to insti tute a crash program to develop such a method. The final procedure utilizes measurement of the volatil ized mercury vapor by flameless atomic absorption (15). The fish muscle is digested with concen trated acids; the mercury is reduced with stannous chloridc-hydroxylnmine and then volatilized at room temperature in a stream of air (Fig ure 3). The air is pumped through a gas coll where the mercury vapor is measured by atomic absorption at 253.7 nm. As little as 0.05 ppm total mercury in the edible portion of the fish can be determined. Sci entists of the Washington labora tories confirmed these results by neutron activation analysis (16). The method was collaboratively studied by nine laboratories, adopted 2CA ANALYTICAL CHEMISTRY. VOL. 44, NO. 13. NOVCMBER 1972 as official by the AOAC, and used for rapid examination of large num bers of fish samples by the field districts and other laboratories (/,'). However, this method deter mined only total mercury, whereas methyl mercury was the actual toxic factor. Dr. Gunnell West 66 of the National Institute of Public Health at Stockholm, who had developed a gas chromatographic method for methyl mercury in several food stuffs (sensitivity of 0.01 ppm), visited FDA, nod her method (IS) was studied at the headquarters' laboratories. Some modifications were made in the procedure, and checks were run between the total mercury and the methyl mercury content of fish. From these and other results, practically all of the mercury in the fish was present as methyl mercury (19). Thus, the method for total mercury was ade quate for FDA's regulatory work on fish. Pesticides end Mobile laboratory By the mid-lOoO's, FDA was deeply involved in analysis of raw agricultural products for residues of the new organic pesticides develops! after World War II. Most of the original procedures were long, tedi ous methods based on classical chem ical reactions aimed at detectin': residues of a single pesticide. Iiir . screening methods involving pm rr and thin-lavcr chroma t ngra \ >t y and finally gas-liquid chromatog raphy were used to examine a sam ple for a large number of residues simultaneously (SO). Time has always b"on critical in FDA work. Examine ion of raw agricultural produc i r , however, posed an even greater time con straint. The FDA inspector would sample a lot of a given raw vegetable at some remote point, usually near the harvest area, and then have m ship the samples by airmail or freight, to the district laboratory If the product did contain excessive pesticide residues, valuable time was lost. To speed pesticide residue analy sis, in 1901 FDA first experimented with mobile laboratories, Standard small house trailers were converted to laboratories by installing appro priate furniture ami ci|iiipim in. The only instruments were sample preparation equipment, a :mple MONS 084101 Report for Analytical Chemists visible spectrophotometer, and pa per and thin-layer chromatographic equipment. Those trailer lubs were not self-contained; they required sever facilities nnd hookups for electricity and wnler. In practice the trailer was transported to some central location near a major grow ing area during the harvest season and operated ns an examining labo- ratory for samples collected from the immediate vicinity. These early trailer laboratories did yeoman work in field examina tion of products for pesticide resi dues and also ns examining stations for physical or sensory analysis of products offered for import into the U.8. ihrough remote border stations. It was soon evident, however, flint they were not adequate for the com plex analytical examinations that needed to be made in t lie field. In IfltVI FDA accept I'd delivery of. brand-new, large custom-built trailer laboratories, nearly 40 ft long and outfitted with the equipment needl'd to perform most chemical analyses in the field. The new labs contained full operating hood space and a gas-liquid chromatograph equipped with electron capture de tector for simultaneously screening raw agricultural products for a large number of pesticides at extremely low residue levels. They still re quired utility and water hookups and had to be transported from one location to another. These new trailers proved to be the key to rapid identification of potential pesticide residue problems. During 1007, for example, the trailer laboratory operating out of the FDA Dallas District office was stationed at Laredo, Tex. Cantaloupes being imported from Mexico contained residues of the pesticide chemical, endrin. Although use of endrin is not permitted on most foods, it is sometimes found in the soil from previous application on nonfood crops such as cotton. Many vine and root crops leach the endrin from the soil during growth. Canta loupes are a major export item for Mexico, nnd the Mexican govern ment became concerned when the problem arose. Meetings were hold between representatives of the Mexi can government (arranged through the V.S. Department of State), V.S. Customs, FDA. and V.S. and Mexi can importers and growers. A crash program was instituted to examine all shipments of Mexican cantaloupes, in which the trailer laboratory at Laredo played a key role. During a 0-week period a total of 1200 samples was examined by the Dallas, Denver, and Now Orleans laboratories of FDA and iho trailer laboratory at Laredo. As a result of the examinations, 100 rail cars of cantaloupes were detained and destroyed. Besides performing large numbers of analyses, the trailer laboratories have helped identify some interest ing new analytical problems. In 1071 the trailer operating out of FDA's Los Angeles District at Nogales, Arias., routinely examined a sample of Chinese peas imported from Mexico and found an unidenti fied pesticide residue. Further in vestigation showed that this residue was a hulogonnlcd orgunoph'^phatr. By use of a variety of instrumen tal techniques at the district labora tory, the residue was finally identi fied as a pesticide not registered fr use in the United States. Ii ap parently had been used provisionally or experimentally in Mexien prinr tn its legal use in the United States and was later granted a temporary tegistration. The FDA New York District i> responsible for one of the larg.-i ports in the world. In 1071 the District converted van-type delivery trucks into self-propelled mobile laboratories to be used directly on the docks to expedite examination of import goods offered for entiy into the V.S. (Figures 4n,b). Al though these vans could be used unis for physical or sensory tests and some minor chemical determnm- Figure 4a. New York District's mobile laboratory at docks tor examination of imports \ A / i rr> I 1 \I ..--J Figure 4b. Inside one ol FDA's new mobile laboratories. Richard Kin;; oi FDA re.'' n- : special features to (left to right) HEW Secretary. Elliot L. Richardson; Assistant Socr.-e. ry for Health and Scientific Affairs. Mertln K. DuVal; and FDA Commissioner. Ch :,ics C. Edwards MQNS 004102  fa's & * ' >.: - v'l 'V..I ;t.. \* ,V'*I RP0(1 tor tulytkl Chmltt. Pye Unicam SP1300 Thabaalo Manual, double-baam unit UV-Vla, flanaa: 190 700nm or 19D*850nm, Four absorbance scales & concentration presentation , High resolution mono chromator Automatic lamp change Double beam recording Second sample position tor turbid solutions Base line compensation Asa *^wwn Resolution to 0.1 nm______ (plug-in additions): Multiple sample handling Digital readout & printer Temperature programming Fluorescence Automation accessories 7SQ S, FlILTON AVE . MT, VMNON.NY. 10SSO a uryioivN ur r*ri. inu. CIKU 174 ON RiADM SERVtCC CARO HONS 004103 Plwiogrtphrt at tha Cerooiat* Haadauadaf* ang Saiaaieh Laboiateoaa. iunougftl W*MeomaCo ,RM<ch Triangla Park.N C. tions, they wore the first truly mo bile lrDA laboratories. They could be driven into a warehouse or along side a ship at berth or parked at any convenient spot near the goods being sampled. This experiment was so successful that FDA has just purchased new mobile laboratories--custom-built, self-propelled laboratory vans, each equipped with n 5000-watt gaspowered generator and pressurized water and sewage collecting systems. They have multichannel mobile telephones for quick communica tion with the district office. Pres ent plans call for these mobile labo ratories to be used for examination of import samples at major ports in the same way that the New York Dis trict uses the converted vans. PCS Problem During the fall of 106$, Japanese investigators (21) reported the out break of a peculiar disease which re sulted from eating rjee oil contami nated with Kanechlor, a mixture of polychlorinated biphenyls (PCB). In 1971 USDA and FDA, in a co operative investigation, found that fish meal, poultry, and eggs had be come contaminated from industrial accidents in which a PCB mixture leaked from heat-exchange equip ment into the food product. Thou sands of hens and broilers were voluntarily destroyed, and adulter ated eggs were seized. PCB's have also migrated into foods from pack aging and other sources. FDA pro posed regulations to control the accidental contamination of foods and to limit PCB residues from environmental or industrial sources (**>. These industrial chemicals, of which there arc 210 theoretically possible isomers, arc used exten sively in electrical insulation, heatexchange liquids, inks, paints, and plnstics. Chlorine may be sub stituted in one or more of the num bered positions of the biphenyl mole cule. s' ' si a' a' s They are commercially produced by chlorination of the parent biphenyl nucleus to certain specified chlorine contents, producing a mixture of isomers with properties similar to those of DDT and its analog*. Hence, any PCB's in a food product will be carried through n typical pesticide determination and may interfere with the interpretation of the gas chromatogram. Because of this and because of alterations in isomeric composition of the PCB mixture through wea thering, metabolism, adsorption, and solubility effects, a fullv satis factory analytical method poses many problems. A procedure ha been developed by FDA chemists and used to separate PCB's from chlorinated pesticides by selectiveelution from a silicic acid column (d). Work is continuing to im prove tins method, since recovery decreases with decreasing chlorine content so that separation of the mono-, di-, and triisomers from DDT and its analogs is not always com plete (24). Drugs and FDA Although FDA spends 39% of its funds on foods, it allocates nearly as much--36%--to drugs. In addi tion to pharmacology, toxicology, and bioavailnbility studies, meth ods are continually being developed to test the safety, purity, potency, and effectiveness of drugs for both human and veterinary use. Until a few years ago, these methods were designed chiefly for use on compos ites, for instance, a sample of 20 tablets. Recent research, however, has shown that the quantity of ac tive ingredient may vary greatly from tablet to tablet or capsule to capsule. These drugs are vised in small amounts in a tablet or capsule in conjunction with a relatively large amount of filler or bind r. and even slight deviations from the labeled amount of active ingredient may markedly change the potency of the drug, presenting a possible hazard to the patient. The trend now is toward individual tablet analysis (ITA), which may require 10, 20, or even more analyses . i single tablets in place of duplicate determinations of n 20-tablet enmposite. Because of the tremendous workload involved in eonventi-tteit analysis at this level, I'DA tin m * I i automated analyses. In mlilii ......... automatic analyzers in the in M districts, the agency has set up National ('cuter for Drug A nab -i- ; ii n. I) Report for Analytical Chemists___________ 99.999951 St. Louis; this installation operates on an assembly-line basis, relying tion to infrared spectrophotometry. The problem was especially difficult mainly on automated and semiauto- because of the minute amount of mated procedures and on calcula material available for analysis. All tion of data by computers and pro of the tests confirmed the identity of grammable calculators. Tkc Cen the substance as creatine mono ter's research unit adapts established hydrate, and none of them revealed methods to automated operation more than a trace of any other sub and develops new procedures as the stance. need arises (85). This led immediately to another One of FDA's most interesting question. The vehicle in which the research studies was the identifica injection form was dissolved was tion of Krcbiozen. Introduced in mineral oil >'<, creatine nemo- 1930 as an agent for the treatment hydrate is not soluble in mineral oil, of cancer, Krcbiozen was said by its even in low amounts. Then, what continuous I producers to be a biological product I derived from the serum of inoculated was the substance in the mineral oil? FDA scientists extracted ihc HIGH OUTPUT | horses. In 1962 after passage of the i Kcfauver-Harria Drug Amendments, its sponsors filed an Investigational mineral oil injections with water and water-ethanol mixtures, evaporated the aqueous fraction, and separated UNATTENDED New Drug Application. When FDA began its investigation, re it chromatographically. Traces of creatinine were detected, as well quests for a sample of Krcbiozen as larger amounts of a chemically OPERATION substance for examination were ignored by the manufactures. Af similar substance which w as judged probably to be l-methylhydaiiiom. ter several months, they did provide Creatine will hydrolyse first to LOW COST an FDA inspector with a single ampul containing a small quantity of material which they said was creatinine and then to 1-mcthylhydantoin upon heating with amyl alcohol and small quantities of al r LONG LIFE Krcbiozen substance. The same sponsors had submitted Krebiozcn samples to the National Cancer kali. During the evaporation of the aqueous fraction of the extract, on odor like that of amyl alcohol hud ' ] Tin ETl Helium Diffusion i Cell Purifier Is e com ] plete equipment, ready '' for continuous production of ultra-pure helium from ` commercial (redes. Total > impurity levels as low as , 112 part per million are possible without the use y of liquid nitrojen-cooled Institute two years earlier, and an infrared spectrum of those samples was available. The melting point, empirical formula, and molecular weight of the substance had been provided by the manufacturer. The infrared spectrum suggested the possibility that the substance might be an amino acid, and since it was somehow associated with been detected, and glc had shown that n-amyl alcohol was present in samples of the mineral oil injection in a concentration that correlated with that of 1-mcthylhydantoin. To duplicate the means by which creatine had been incorporated in the mineral oil, FDA scientists dis solved creatine in amyl alcohol at the proper concentration; to 50 ml _ | absorbents. horse blood, FDA scientists pro of this solution was added pellet of I Ultra pure helium Is now ; i beiitf used extensively in | gae chromatography. ceeded on the hypothesis that it might be a known amino acid pres ent in blood. By examining authen KOH, and the solution was refluxed. The reflux waa sampled at intervals, and the sample checked by tic. u. transistor processing, iil orystaf growing atmos tic spectra of amino acids, it waa discovered that the Krcbiozen spec After 30 min, all the creatine had hydrolyzed to creatinine plus u trace pheres and other services trum was identical with the pub of 1-mcthylhydantoin; by 24 hr, where high purity helium lished spectrum of creatine mono the material remaining was virtually facilitates parts per bil hydrate, a well-known, readily avail all 1-mcthylhydantoin. Upon anal lion accuracy in critical able amino acid which is present in ysis, 1 ml of this end product be analyses. Write for additional In blood. To prove that the substance given haved exactly like the product fur nished by the manufacturer. Tic formation or engineering to FDA was the same as the Na showed that samples of the original consultation. tional Cancer Institute material product contained small traces of Electron Technology 626 Schuyler Ave., Kearny. N.J. 07032 Or call (201) 998-8100 and therefore was creatine mono hydrate, FDA scientists in conjunc tion with members of university faculties examined the sample by X-ray diffraction, mtVHS spectrom creatinine plus 1-mcthylhydaiuoin; for further identification, 1-nwthyihydantoin was isolated from the oil by paper chromaiogruphy, rcovered from the paper, and incor etry, microscopic crystallography, porated in a micro lvBr disk. The a, ELECTRON TECHNOLOGY I thin-layer and paper chromatog- infrared spectrum was identical A UNIT OF CSTERUNB CORPORATION 1 raphy, and molting point, in addi with that of pure 1-methylhydanioin ( ( CIRCLE M ON READER SERVICE CARO 1 HONS 064104 Ruport for analytical Chiwiiti f TM --1 under the game conditions. In this uuinncr, It was dcmonMrntcd that plication of instrumental methods \ to analytical chemistry, comprising j / ! the substance alleged to be a new 91 hr of lecture, 62 hr of recitation, drug, Krebioscn, was actually cre and 204 hr of laboratory work. The atine monohydrate and that some University gave each student an inmplcs of Krebioscn injection con academic grade according to its tained l-methylhydantoin, a deriva usual criteria and awarded graduate , tive of creatine. credit at its own discretion. Several positions in each course were re- j Keeping Current served for scientists from other ; As with all scientists, the possibil government agencies, industry, the I ity of technical obsolescence of FDA's analytical chemists must al*;iy# bo couH'irml. T< I'dmliy' obsolescence, several tactics have academic world, and foreign coun- j tries. By April 1660 the majority if Ff> t' apMlylic.'il chemist? had I completed the course, and the Insti CD 3000 SYSTEM been devised. FDA scientists are tute changed its program to special encouraged to be active in profes sional societies, to take part in sci entific meetings and seminars, and to cnnlinuo their education, often at courses of one, two, or three weeks on such topics as liquid chromatog raphy, use of computers in the ana lytical laboratory, frontiers in ana QUANTITATIVE TLC the agency's expense. Because the lytical techniques and photochem standard curricula do not always istry, and fluorescence and phos meet FDA's needs, the agency joined with Georgetown University, Washington, D.C., in 1904 to set up the "FDA Institute for Advanced Analytical Chemistry" (26). The University provided three labora tories for the exclusive use of the course plus full-time and part-time faculty members. Some of the phorescence spectroscopy. In May 1966 a Science Advisor Program was initiated for the bene fit of the field districts. In this program a professor of chemistry or microbiology (or both) on the faculty of a university within easy commut ing distance of the district is em ployed as a consultant and advisor Typical Quantitations: Aliphatic Lipids Alkaloids Amino Acids Amniotic Fluid Estrlol Amphetamines Anelgssics Antihistamines Antipyretics analytical instrumentation (mass to the laboratory staff and manage Antirheumatics spectrometer, computer! was fur ment of the district (Figure 5). Se Bacterioititics/Bacteriocidits nished by the University, and an lection of advisors is based on activ Barbiturates additional $222,000 worth of instru mentation was provided by FDA, including gas chromatographs, atomic absorption equipment, all types of spectrophotometers, nu ity in both teaching and research at the university and on direction of graduate study in an area in which analytical chemistry or analytical microbiology is a principal part of Bile Adds Blood/Urine Cortisol Carbohydrates Cholesterol Esfriol in pregnancy urine Insecticides clear magnetic resonance equipment the investigation. Malto-sacchsrides with a time-averaging computer, Since passage of the 1900 Food Mandelie Acid & Derivatives I and polarographs. The curriculum and Drug Act, both the problems to Phenols f emisistcd of a 12-week intensive be solved and the means for solving Phospholipids course of advanced theory and ap- them have advanced by several Polymers Porphyrins Pyrethins ( Sulta-lype Drugs Testerone in urine Urinary Cetacholamines Urinary Purinst Urina-17 Ketosteroids \ 1 ( Il Complete date on request. SCHOEfffl INSTRUMENT CORP. 24 Booker Si.. Westwood. N. J. 07875, (201) 884-7263. Telex 134356. In Europe: SchoelfeJ In strument GmbH, 2351 Treppenkemp, Celsiusstrasst 5, W. Germeny (04323! 2021. Telex 299660. s im e o snow \* 5- Chemist Larry Alber and Chicago DistrlctScienceAdvisor, Donald Smith of '' " wottom University, have interfaced a gas chromatograph with a computer and *1 ,,Jbed a program for online computation of analytical data T! ASCHOEFFEL ` CmClC 193 ON REAPED SERVICE CARO ANALYTICAL CHEMISTRY, VOL 44, NO. 13. NOVEMBER 1972 3J A T Report for Analytical Chamlata orders of magnitude, in the same way that the acceptable level of sensitivity has dropped from the milligram to the nanogram or picogram level. Tor effective protec tion of the consumer, FDA must continue to use every possible re source, including more* adequate (6) A. D. Campbell and J. T. Fmikhouacr, J. Aw. OJftc. Anal. Chem., *9, 730 (1000); It. M. Kpplev, h. Siolofr. and A. D. Campbell, tbit}., 51, 07 (J 90S); A. E. Pohlnnd, I,. Yin, and J. G. Dantzman, ibid., 53, 104 (1070). (7) L. StoIofT, A. I). Campbell, A. C. Beckwith, R Xeshcim, J. 8. Winbuah, Jr., and O. M. Kordhnm, Jr., J. A mar. Oil Ghent. Sac., 46, 078 (1960). Inoue, Kumamoto Med. J,, 14, wi (1901). (15) R. K. Munna and I). C. Hnllititd / Am. Oftic. Anal. Chem., 54, 202 (1971). (10) M. IfeiUmnn and R. Simmon, ,6' 55, 960 (1972): J. T. Tanner, M. ])' Friedman, D. N. Lincoln, L. A. t'nnl. and M. JaiTec, Science, 173, in (1972). ' (17) L. It. Kamps, It. Carr, nnd H. Mill,-, budgets, better qualified personnel, moro Advanced instruments, and (8) M. J. Verrett, J.-P. Mnrliac. and J. McLaughlin, J. Am. Oftic. Anal. Cltcm., 47, 1003 (1964). Bull. Environ. Contam. Toxicol., 6, ji', prene (1972). (18) G. Westfib, Ada Chem. Brand., 2ft 3 newer techniques. But one of its (9) J. V. Rodrickn, K. R. Uenery-Lnzan, 2131 (1966); ibid., 21, 1790(19071. ' \ chief tools will continue to be ana A. D. Campbell, L. StoIofT, nnd M. J. (19) L. R. Kampa and B. McMahon. .1 lysin'! chemistry. Verrelt, Vii/ifn, 217, flC.H (Htfisi Oftic. .1 Cbrw . ?'. vi (10) L. StoIofT, J. O. Dnntiman, and J. (20) P. A. Mills, J. II. Onlrv, and it. \ Wegener, J. Amer. Oil Chem. Sac., 49, Gaither, ibid., 46, 180 (190:1); "ntfirj.,| RtfiriMM 204 (1972). Method* of Annlvsia," llth ed., t!*7t (]) FDA Annual Report 1071, FDA Pap., 9 (10), 4-5 (December 1P71--Jrimmry 1079). (2) "United Sintra Pharmacopeia," 18th (11) P. J. Andrello* and G. R. Reid, J. Am. OMc. Anal. Chem., 47, 801 (1964); L. StoIofT, ibid., 50, 354 (1907). secs. 29.001-29.027, (21) M. Kuratsunc, T. Yoshimurn, .1. Malaunnkn, and A. Ynm.'icm*hi. HSMHA Health Kept., 86, 108-1 ,|<7I rev., Mark Printing Co., Keeton, Pa., (12) A. Curley, V. A. Sediak, E. F. (22) Fod. Ii(pi*l.,i7,5705 (March IK. M72v 1070. (3) "National Formulary." I3lhcd., Mack Printing Co., Enaton, Pn., 11)70. Girling, It. E. Hawk, W. F. Bnrthei. P. E. Pierce, and W. Jf. Likoekv, Science. 172,65(1971). (23) J. A. Armour and J. A. Burke. J Aw. Oftic.. Anal. Chem., 53, 701 (1970*. (24) H. T. Mnaumoto, ibid., 55, in ore** (4) "Official Methods of Analysis," I Ith (13) A. K. Klein, J. Ass. Oft?e. Anal. (1072). ed., Association of Official Analytical Chemists, Washington, D.C., 11*70. (6) It. Allcrrrfl nnd It, U. A. Cnrnnghan, Chem., 35, .537 (19.52); "OfTIcial Meth ods of Analysis," 11th cd., 1970, secs. 25.058-2ft.0ta. (23) \V. B. Furman, FDA By-l.mv,, i (3), 113(1970). (26) .li. P. Eiduson, J. Chem. Edur., 43, Chm. M.t M) (1903). <1 (H) M. Uohida, K. Hirakawa, and T. 617 (1900). 'ti Helen L. Reynolds is an editorial officer in the Bureau of Foods and direete the technical editing program for the Bureau of Foods and other unite of the Food and Drug Adminis tration. A notice of Washington, D.C., she received her bachelor's degree in chemistry from Dunbarton College and her master's in public adminis I tration from American University. She joined the FDA staff in 1960 after work at the National Institutes of Health and several scientific associa tions. Miss Reynolds is Editor' of the Journal of the AOAC and FDA By-Lines and has served as consulting editorfor several monographs. Hyman P. Eiduson is Director of the Field Sciences Branch at FDA and coordinates the compliance, re search , and other laboratory activities of the 18 FDA field laboratories. lie received his BS degree from the Uni versity of Buffalo (note State Uni versity of New York at Buffalo) and joined FDA in 1946. He teas in strumental in setting up the FDA Institute of Advanced Analytical Chemistry at Georgetown University in 1964- The course consisted of an intensive 18-week program of lectures and laboratory sessions (`'.-l natmnij of an Institute,1' J. Chem. Edur., 43 {11),617 {1966)). MONS 0 8 4 1 0 6 ;*T1 John R. Weatherwax is Labora tory Director of the Los Angeles Dis trict of the Food and Drug Adminis tration. After on interruption in his education by military duty with the U.S. Army, including 16 months in Korea, ;l/r. ircafhcnrox obtained his 1)S deyicc in chemistry from San Francisco State College. He joined FDA as a chemist with the San Fran cisco District and later transferred to the Dallas and Los Angeles District.1}. He spoil several years at headquarters in Washington, D.C., before return ing to Los Angeles as Laboratory Director. n \ >;* Donald D. Dechert, analytical chemist {Research Coordinator) for FDA's Los Angeles District, received his BA degree in chemistry from fhe University of California al Riverside. He joined FDA as a chemist in Wii! and was assigned as Los Angeles District Research Coordinator in Mr. Dechert coordinates and imple ments the research activities to snppt.. the regulatory activities of the fii*t i. He. also works closely with the Dis trict's science advisors to cnini'i, -- i> < scientific capabilities of the l)v't<,. Mr, Dcrhert in note inrrstimvr": methods of nndtielannits analysi.-. \ 34 A ANALYTICAL CHEMISTRY, VOL. 44. NO. 13. NOVEMBER )972