STANFORD UNIVERSITY MEDICAL CENTER STANFORD, CALIFORNIA 94305 « (415) 321-1200 Exr. 5785 STANFORD UNIVERSITY SCHOOL OF MEDICINE Department of Anesthesia November 30, 1973 Professor Joshua Lederberg Department of Genetics School of Medicine Stanford University Stanford, California 94305 Dear Dr. Lederberg: Thank you for including my laboratories in the group which could be served by a GC/HRMS facility. As you know,.- Dr. Cohen and I have our own GC/MS/ Computer System. Our use of the pro- posed facility would be limited to those times when it is necessary to use high resolution ot identify a metabolite. I would estimate a need for three GC/HRMS and three HRMS Spectra per year. My work is entirely supported by the National Institutes of Health. Sincerely_yours ly Qt} James R. Trudell, Ph.D. JRT: rw Jab HOV 27 We VETERANS ADMINISTRATION HosPITAL 3801 MIRANDA AVENUE PALO ALTO, CALIFORNIA 94304 IN REPLY REFER TO: November 26, 1973 Professor J. Lederberg Department of Genetics Stanford University School of Medicine Stanford, California 94305 Dear Prof. Lederberg: Dre Allan Duffield of your department has informed me that you plan to obtain additional apparatus that would provide high resolution GC/MS as a service to the Stanford community. We have in the past used the hospitality of your department in the identification of metabolites and derivatives of phenothiazine drugs and cannabinoids by GC/MS. Originally, we had the collaboration of Dr. B. Halpern and more recently Dr. A. Duffield, who was instrumental in helping us with some of our problems. - Our department would indeed be most interested in availing ourselves of GC/MS analyses in the course of our current NIH projects which again are concerned essentially with drug metabolism and the isolation and characterization of unknown drug derivatives. As a rough estimate, I would think that we may-be interested in the analyses of about five samples per months two of which will require high resolution MS. . I certainly hope that your project to acquire the sophisticated new instrumentation you are seeking will be successful. Sincerely yours, Irene S. Forrest, Ph.D. Chief, Biochem. Research Lab. (151F) ISF: jr Show veteran's full name, VA file number, and social security number on alt correspondence. L. ‘2 P OFFICE MEMORANDUM e¢ STANFORD UNIVERSITY © OFFICE MEMORANDUM @ STANFORD UNIVERSITY @e OFFICE MEMORANOUM DEC 3 4973 Date: November 30; 1973 To Joshua Lederberg From: «f. Rabinowitz, Ph.D. D.I. Wilkinson, Ph.D. Suosect: RE: NIH GC/HRMS Proposal Research carried out in this department has strongly implicated a role for the prostaglandins in the etiology of psoriasis (E. M. Farber, K. Aso, 32nd Annual Meeting, American Academy Dermatology, Chicago, I11., Dec. 1973; E. M. Farber et al, J. Invest. Derm.,in preparation; E. M. Farber et al, Nature New Biology, in preparation). The prostaglandins are a class of Coo fatty acids, having molecular weights near 350 and basal tissue con- centrations in the nanogram and picogram per gram range. The prostaglandins are presently detected by radioimmunoassay, bioassay and mass spectrometric techniques, among others. There is considerable controversy concerning the method of choice for measurement of absolute amounts of prostaglandin in various tissues. In particular, it has been suggested that mass spectrometric techniques yield more accurate quantitative assays than radioimmunoassay techniques (Adv. Biosciences, 9, 71-123, 1973, Ed. G. Raspé, S. Bernhard, Pergamon Press, N.Y.). Radioimmunoassay techniques are currently in use in our laboratories, and the addition of mass spectrometry capability would greatly increase the definitiveness of our studies, as well as make available to us a powerful tool for the study of prostaglandin precursors and metabolites. Work to date has been supported in part by NIH Grant No. AM 15107. borat DVB even Deo b Whee I. Rabinowitz, Ph.D. O . I. Wilkinson, Ph.O. Department of Dermatolo eae of Dermatology 4 IR: DIW:ss INAINVYOWIW 351ddO © ALISYUTAINM GYOANVLS © WNGNVYOWIW 321ddIO © ALISUZAINA QYOINVIS © WNGNVYOWAW ad1ddO © ALISUZAINN GUOANVIS © JRE OFFICE MEMORANDUM @ pec 3. 1973 Date: November 30, 1973 Joshua Lederberg, Department of Genetics T ° Carl Djerassi, Department of Chemistry From Eugene D. Robin, M.D., Department of Respri atory Medicine Susiect; YOUX memo of November 20, 1973 describing a proposed GC/HRMS facility. ¢ I have applied to the NIH for a continuation of my research grant, Adaptations To 0» Depletion in which I have proposed to measure the redox state of NAD +/ NADH and NADPt/NADPH by measuring the ratio of oxidized to reduced redox pairs using g gas chromatography/mass spectrometry. These analyses will be conducted with the assistance of Drs. Alan Duffield and Wilfred Pereira of the Department of Genetics. I welcome the opportunity to have a GC/HRMS facility available on campus to support the GC/LRMS available in the department of genetics. The facility you propose to establish will be of importance to us in those instances where assignment of molecular composition to fonized fragme-ts is crucial for wass spectral interpretation. I would anticipate using this service between one and two times a month. , Sincerely yours, a » “oven, M.D. Professor of Medicine and Physiology EDR:ods JA? STANFORD UNIVERSITY © OFFICE MEMORANDUM e¢ STANFORD UNIVERSITY © OFFICE MEMORANDU?A LONVUOWAW HIIddO © ALISUTAINN GYOUNVAS © WNONVYOWSW aatdgO © ALISUZAINN GYOUNVLS © WNONVYOWAW H2IddO © ALISUZAINN GNOENVIAS @ NOV 30 1973 VETERANS ADMINISTRATION HOSPITAL 3801 MIRANDA AVENUE PALO ALTO, CALIFORNIA 94304 November 28, 1973 REFER 10: Dr. Joshua Lederberg Department of Genetics Stanford University School of Medicine Palo Alto, California 94305 Dear Dr. Lederberg: I should be very pleased if you were able to obtain through the National Institutes of Health a GC/MS facility which could be shared jointly by members of the Stanford University faculty. At present, I am being funded under grant DA-00424-01 for a study of the metabolism of ma.ihuana. We have made significant progress in our methods of extracting metabolites, in isolating new ones by thin-layer chromatographic techniques, and by purify- ing them to some degree as determined by GLC. The big bottleneck has been the lack of ready access to a GC/MS set-up which would permit further characterization of the metabolites. Our needs would be primarily for GC/low resolution MS, for which we have extensive need, perhaps the analysis of 15-25 samples per month. Depending on the outcome of these analyses, we might have 1 to 2 samples per month requiring GC/high resolution MS. We anticipate having little need for high resolution MS without GC because of the fact that our samples are isolated from complex mixtures and are nearly impossible to purify. If there is any way in which I could assist in helping obtain such a facility for the University, please let me know. Sincerely yours, Leo E. Hollister, M.D. ~, Associate Professor of Medicine LEH: bh Show veteran's full name, VA file number, and social security number on all correspondence. 130° . STANFORD UNIVERSITY HOSPITAL Pharmacy Department Date September 5, 1973 To: Dr. J. Lederberg, Director Department of Genetics _ From: Hiram H. Sera, Director Lh (fe Subject: Drug Analysis Service with Gas Chromatograph and Mass Spect- rometer, . I wish to express our appreciation to your department for assisting us in identifying a drug sample submitted to us from the Fl patient tare area, BACKGROUND: . The patient on E1A with G.I, disturbance, joint pains and occasional spike temperature was found to possess an unidentified medication in a plastic vial and was found to have self-administered the drug intramus- cularly while in the hospital, The house staff was notified and the drug sample was submitted to us for immediate identification, Through my previous association and knowledge of Drs. Summons' and W, Perieras'’ (in Dr. Duffield's instrumentation research laboratory) work with gas chromatograph and mass Spectrometer, I had taken the liberty to request their assistance in the identification, In an hour, the determination was made and the drug was found to be Pentazocaine or Talwin which is a Synthetic analgesic used commonly in this hospital in tablet and injection forms. Since we do occasionally receive similar requests from physicians, I wish to call on your staff again in the future, Thank you. HHS: lh ce: Mr. John Williams Dr. Roger Summons Dr. W. Periera Dr. A. Duffield 78/ OFFICE MEMORANDUM e¢ STANFORD UNIVERSITY © OFFICE MEMORANDUM e¢ STANFORD UNIVERSITY @ OFFICE MEMORANDU?PA Date: November 26, 1973 To: Joshua Lederberg, Department of Chemistry Carl Djerassi, Department of Chemistry From : Sumner M. Kalman SuBsect: Mass Spectrometry, Your Memo ‘of November 20, 1973. A central facility for mass spectrometry and GC/MS would be highly desirable from my point of view. We often need to identify metabolites of drugs that interfere with our assays, and that represent research problems as well. Frequently we need to check the purity of a reference material which is in short supply. I have received much heln from both your laboratories in the past and would welcome the opportunity to use an expanded facility. For many of our prcblems low resolution MS is satisfactory and I hope you mean to provide this service too. , With respect to your questions I anticipate that (1) Yes. (2) We would probably use GC/MS once a month or more. We would use MS at about the same rate. (3) Yes. Sincerely yours, oyun tt. (elem, AD Sumner M. Kalman, M.D. Professor of Pharmacology Director, Drug Assay Lab VYSOWAW FI1ddO © AAISSTAINN GYOUNVAS @ WNONVYOWEW FdlyO © AAISYZAINA G¥YOQUNYAS @ WNONYHOWAW BolddO © ALISUZAINN GYOENYAS ¢ a ABR PN res, OFFICE MEMORANDUM e STANFORD UNIVERSITY © OFFICE MEMORANDUM @ STANFORD UNIVERSITY @© OFFICE MEMORANOUM To From SuBJEcT: DEC 3 1973 Date. 3 December 1973 Joshua Lederberg Jack Barchas GC/HRMS Our thanks to you and Alan Duffield for inquiring of our interest in the proposed GC/HRMS. We would find it quite useful, as we are currently applying for funding for a quadrupole mass spectro- “meter for mass fragmentography studies. With such a unit, there would be many times when the capability of the HRMS instrumentation woulu be valuable in structural elucidation. We would expect very heavy utilization of our instrument if we were to-obtain the funding, and, therefore, would expect to make considerable use of the proposed GC/HRMS, which is an essential ancillary tool. The GC aspects of the instrument would be valuable, since we would expect to be studying a number of unknowns and the GC separation would be an integral part of that process. Our work is supported by NIMH, ONR, NASA, and the Alcohol Abuse division of HEW. y JDB/rs — 733 WNONVYOW3W 351dIO © ALISUTAINN GYOSNYVIS «© \TONVEOWIW 3D1ddO © ALISUTAINM GYOINVLS © WNAONVYOWSW 3Dd1sdO © ALISYBAINN GYOINVIS e NOV 30 1978 NATIONAL AERONAUTICS AND SPACE ADMINISTRATION AMES RESEARCH CENTER MorFeTT FIELD, CALIFORNIA 94035 REPLY TO ATINOF: LLPE: 239-9 November 28, 1973 Professor Joshua Lederberg: Department of Genetics School of Medicine Stanford University Stanford, CA 94305 Dear Professor Lederberg: I was delighted to learn of your proposed plans to upgrade your mass spectrometry capabilities by providing routine high rez olution mass spectrometry (HRMS) and combined gas chromatography/ high resolution mass spectrometry (GC/HRMS). Such a service could be of inestimable value to our program. As you know we are developing gas chromatography/high resolution mass spectrometry facilities for NASA's interests. In particular we are modifying our equipment in order to determine carbon and nitrogen isotopic compositions of organic molecules. If available we would use your proposed facilities for our routine GC /HRMS analysis of biologically significant molecules which are sought in our program. Most of our work requires GC/HRMS as opposed to HRMS. In addition, we are also most interested in computer programs which aid in mass spectral interpretations. Although we have a few of our own programs, we would be most eager fo upgrade our own interpretation capabilities through use of programs from your facility. Our work thus far has been supported solely by NASA; we are not supported at present by NIH. I hope that our expression of interest will be of use to you in obtaining funding for a potentially most useful analytical facility. Sincerely yours, a , _ . a e me ete’e Ce. ee ateeeeebel Coe Keith A. Kvenvolden Chief, Chemical Evolution Branch 134 OFFICE MEMORANDUM e To From SusJECT: NOV 29 1973 Dare: November 28,. 1973 Joshua Lederberg, Ph.D. $331 William R, Fair, M.D. $287 Use of facilities for high resolution mass spectral analysis with gas chromatography. As your memo of November 1973 requested, we have answered the questions concerning our interest in GC/HRMS. 1. 3 This service would be of definite value to us in two projects currently being investigated in our laboratories. a) The identification, distribution, and biological significance of the prostatic antibacterial factor (PAF). Our preliminary experiments indicate tl.at this is a basic polypeptide, perhaps attached to a divalent metal such as zinc. b) This service would also be of value in the determination of the urinary polyamine levels in patients with various genitourinary tract malignancies. Our initial experiments along this Jine indicate that there is significant elevation of polyamines in patients with prostatic carcinoma. The use of GC/HRMS would enable a more precise quantita- tion of these differences and enable us to expand our research into other areas concerning the biochemical significance of the polyamines. I would estimate that on the PAF project we would use approximately 2-4 samples per month and perhaps 10-12 samples per month on the polyamine projects. Both of these projects would require the use of GC/HRMS. A portion of our research on the PAF is currently supported by a grant from the NIH. The amount of this grant is $36,698, and this grant will terminate on December 31, 1974. 135 a CONVSOWSW JDdiddO © ALISUTAINN QUOANVAS @® WNONVUOWAW JIidsIO © ALISUTAINN QHOSNVIS © WNONVYOWSW FI1dO © ALISYZAINN QYOANVIS ¢ STANFORD UNIVERSITY © OFFICE MEMORANDUM © STANFORD UNIVERSITY #® OFFICE MEMORANDUM