Toxicologie

<p>Applications Azocyclotin is an organotin aracacide used in the control of mites. Azocyclotin showed weak antifeedant activity against other insects such as Spodoptera littoralis.<br> Not a dangerous good if item is equal to or less than 1g/ml and there is less than 100g/ml in the package<br>References Hammann, I. et al.: Pflanzensch.-Nach., 31, 61 (1978); Ascher, K.R.S.: Naturwissenschaften, 67, 312 (1980);<br></p>

<p>Applications Phosalone is a organophosphate compouund used as insecticide and acaricide. Phosalone is a weak inhibitor of acetylcholinesterase.<br> Not a dangerous good if item is equal to or less than 1g/ml and there is less than 100g/ml in the package<br>References Munj, A.Y., et al.: Pestol., 36, 35 (2012); Andrascikova, M., et al.: Food. Add. Contamin. Chem. Anal. Control. Exposure. Risk. Assess., 30, 286 (2013);<br></p>

<p>Stability Light Sensitive<br>Applications Tacalcitol Monohydrate is used as a vitamin D analog used in combination with Imatinib (G407000) in the therapy of non-small cell lung cancer. It is a COVID19-related research product.<br> Not a dangerous good if item is equal to or less than 1g/ml and there is less than 100g/ml in the package<br>References Schindler, T., et al.: Science, 289, 1938 (2000), Drucker, B.J., et al.: N. Engl. J. Med., 344, 1031 (2001),<br></p>

<p>Applications Metazachlor Oxalic Acid-d6 is deuterium labelled form of Metazachlor Oxalic Acid (M226230), which is a chloroacetanilide herbicide metabolite that has been detected in surface water and groundwater from urban surfaces runoff.<br>References Reemtsma, T., et al.: Water Res., 47, 5535 (2013);<br></p>

<p>Applications It is listed as a known human carcinogen. Used in manufacturing of dyes, as antioxidant in rubber.<br> Not a dangerous good if item is equal to or less than 1g/ml and there is less than 100g/ml in the package<br>References Dong, Y., et al.: Bioorg. Med. Chem. Lett., 20, 4085 (2010), Vassiltsova, O., et al.: J. Nanosci. Nanotechnol., 10, 1635 (2010), Garcia-Lavandeira, J., et al.: Anal. Bioanal. Chem., 397, 751 (2010),<br></p>

<p>Applications 4,4'-DDE - d8 is a metabolite of DDT - d8 (D434197), a synthetic organochlorine insecticide that functions by opening sodium ion channels in the insects’ neurons, causing them to fire spontaneously which in turn leads to death. 4,4'-DDE - d8 has shown to have endocrine disrupting effects on gonadotropin hormones in pituitary gonadotrope cells.<br>References Saschenbrecker, P.W.: Can. J. Comp. Med., 37, 203 (1973); Balkew, M. et al.: Paras. Vect., 3, No pp. given (2010); Kikankie, C.K. et al.: Malaria J., 9, No pp. given. (2010); Battu, R.S. et al.: Sci. Total Environ., 78, 173 (1989); Zhou, J., et. al.: Environ. Toxicol. Phar., 37, 1194 (2014)<br></p>

<p>Applications A reactive metabolite of Lapatinib (L175800) which is associated with various drug toxicities. Lapatinib is metabolized mainly by P450 3A4 to form O- and N-dealkylated metabolites.<br>References He, K., et al.: Chem. Res. Toxicol., 11, 252 (1998), Rusnuk, D., et al.: Cancer Res., 61, 7196 (2001), Li, X., et al.: Drug Metab. Dispos., 37, 1242 (2009),<br></p>

<p>Applications Isotope labelled 1’-Hydroxy Midazolam (H948424), metabolite of Midazolam (M343000).<br>References Dundee, J., et al.: Drugs, 28, 519 (1984), Galetin, A., et al.: Drug Metab. Dispos., 30, 1512 (2002), Uchaipichat, V., et al.: Drug Metab. Dispos., 34, 449 (2006), Lewis, B., et al.: Biochem. Pharmacol., 73, 1463 (2007),<br></p>

<p>Applications 5-Methyl-N-[2-(4-sulfamoylphenyl)ethyl]-1,2-oxazole-3-carboxamide is a reagent used for the synthesis of glisoxepid (G410600). Glisoxepid is used as an antidiabetic drug. Glisoxepid is a sulfonylurea derivative used in the treatment of diabetes mellitus type 2.<br>References Schulz, M., et al.: Pharmazie, 58, 447 (2003), Viswanathan, C., et al.: Pharm. Res., 24, 1962 (2007), Drees, J., et al.: Clin. Chem., 55, 126 (2009),<br></p>

<p>Applications N-(3-((2-Chlorothiazol-5-yl)methyl)-5-methyl-1,3,5-oxadiazinan-4-ylidene)benzenesulfonamide is an impurity of Thiamethoxam (T344180) which is a neonicotinoid insecticide.<br>References Oliver, J., et al.: J. Environ. Horticult., 28, 135 (2010), Ghosh, A., et al.: J. Entomol. Res., 34, 35 (2010), Chem. and Eng. News 90: 10 (2012)<br></p>

<p>Applications An antithrombotic. A platelet aggregation inhibitor.<br>References Leblonde, G., : Biochem. Pharmacol., 27, 2099 (1978), O’Brien, J.R., et al: Thromb. Res., 13, 245 (1978), Katsumura, T., et al.: Angiology, 33, 357 (1982),<br></p>

<p>Applications Labelled Azathioprine (A803350). An immunosuppressive antimetabolite. Also active as disease modifying antirheumatic drug (DMARD).<br>References Mitrou, P.S., et al.: Arzneim.-Forsch., 29, 483, 662 (1979), Ding, T.L., et al.: Drug. Metab. Dispos., 7, 373 (1979), Chan, G.L.C., et al.: Pharmacotherapy, 7, 165 (1987), Sandborn, W.J., et al.: : Scand. J. Gastroenterol., 33, Suppl. 225, 92 (1998,)<br></p>

<p>Stability Hygroscopic<br>Applications 1-Amino-3-Hydroxybenzene is used in the preparation of inhibitors of mammalian carbonic anhydrase isoforms. Also used in the preparation of quinoline tethered fluorescent carbon dots for regulated anticancer discovery.<br> Not a dangerous good if item is equal to or less than 1g/ml and there is less than 100g/ml in the package<br>References Carta, F. et al.: Bioorg. Med. Chem., 21, 1564 (2013); Karthik, S. et al.: Chem. Comm., 49, 10471 (2013);<br></p>

<p>Applications Debenzoic Acid Bromotelmisartan-d4 is the labeled analogue of Debenzoic Acid Bromotelmisartan (D289630), an impurity of Telmisartan (T017000), an angiotensin II receptor antagonist.<br>References Wienen, W., et al.: Brit. J. Pharmacol., 110, 245 (1993), Neutel, J.M., and Smith, D.H.G.: Adv. Ther., 15, 206 (1998)<br></p>

<p>Impurity Tenofovir Impurity<br>Stability Light Sensitive<br>Applications An impurity of Tenofovir (T018500). Tenofovir is an acyclic phosphonate nucleotide analogue and reverse transcriptase inhibitor. It is used as an anti-HIV agent.<br>References Peng, J., et al.: J. Clin. Pharmacol., 46, 265 (2006), Seminari, E., et al.: J. Antimicrob. Chemother., 60, 831 (2007);<br></p>

<p>Applications Iprovalicarb is a systematic fungicide. Iprovalicarb is used for the control of pathogenic fungi from the oomycetes class in grapes, potatoes, tomatoes and other crops.<br>References Stubler, D. et al.: Pflanzensch.-Nach. Bay., 52, 33 (1999); Stenzel, K. et al.: Bright. Crop Prot. Conf. Pests Dis., 2, 367 (1998);<br></p>

<p>Applications A metabolite of new designer drug α-Pyrrolidinopropiophenone (PPP). α-Pyrrolidinophenones like 4'-Methyl-α-pyrrolidinopropiophenone (MPPP), 4'-Methoxy-α-pyrrolidinopropiophenone (MOPPP), 3',4'-Methylenedioxy-α-pyrrolidinopropiophenone (MDPPP) and 4'-Methyl-α-pyrrolidinohexanophenone (MPHP) are new designer drugs which have appeared on the illicit drug market. Controlled substance.<br>References Bryant, S., et al.: Clin. Pharm., 1983, 2, 525 (1983), Kalix, P., et al.: Biochem. Pharmacol., 35, 3015 (1986), Maurer, H., et al.: J. Anal. Toxicol., 24, 340 (2000), Kraemer, T., et al.: Drug Metab. Dispos., 2000, 28, 339 (2000),<br></p>

<p>Impurity Esomeprazole Impurity 16<br>Applications Omeprazole (O635000) impurity. Esomeprazole Impurity 16.<br></p>

<p>Applications BMS 833923 is an antagonist of smoothened, a key hedgehog (Hh) pathway regulator.<br> Not a dangerous good if item is equal to or less than 1g/ml and there is less than 100g/ml in the package<br>References Brechbiel, J., et. al.: Cancer Treat. Rev., 40, 750 (2014); Cortes, J., et. al.: J. Natl. Compr. Cancer Netw., 11, 10 (2013)<br></p>

<p>Applications Chlorflurenol-methyl is an auxin polar transport inhibitor that effects elongation growth of the excised fourth internode of tulips. Chlorflurenol-methyl is a pesticide.<br>References Wegrzynowicz-Lesiak, E., et al.: J. Hort. Res., 21, 31-39 (2013);<br></p>

<p>Impurity Atazanavir Impurity 1<br>Applications An epimeric impurity of Atazanavir, novel azapeptide HIV protease inhibitor. Atazanavir Impurity 1<br>References Chitturi, S.R. et al.: J. Pharmac. Biomed. Anal., 55, 31 (2011);<br></p>

<p>Applications Fensulfothion Sulfide is a metabolite of the insecticide fensulfonthion (F265490), an inhibitor of cholinesterase activity.<br> Not a dangerous good if item is equal to or less than 1g/ml and there is less than 100g/ml in the package<br>References Solly, S.R.B., et al.: New. Zea. J. Agri. Res., 14, 88 (1971); Hansch, C., et al.: Biochem. Toxicol. Insectic. Proc., 33 (1970);<br></p>

<p>Stability Hygroscopic<br>Applications Cotarnine Chloride is an oxidative degradation product of the drug Noscapine.<br>References Johansson, M., et al.: J. Pharm. Biomed. Anal., 7, 1055 (1989), Ukhin, L., et al.: Chem. Nat. Compds., 40, 156 (2004),<br></p>

<p>Applications 3,3'-Iminobis(N,N-dimethylpropylamine) is used as a reagent in the synthesis of a novel class of anticancer agents called antracenylisoxazole lexitropsin conjugates. 3,3'-Iminobis(N,N-dimethylpropylamine) is also part of a group of stabilizers (Hindered Amino Stabilizers) that prevent the thermo-oxidative degradation of polypropylene.<br> Not a dangerous good if item is equal to or less than 1g/ml and there is less than 100g/ml in the package<br>References Gijsman, P. &amp; Gitton-Chevalier, M.: Polym. Degrad. Stabil., 81, 483 (2003); Han, X., et al.: Bioorgan. Med. Chem., 17, 1671 (2009);<br></p>

<p>Applications 4-Phenylphenol is a reagent used in the synthesis of pyrrolo[1,2-c]imidazole dione derivatives as selective serotonin 5-HT1A receptor agonists with antinociceptive activity.<br> Not a dangerous good if item is equal to or less than 1g/ml and there is less than 100g/ml in the package<br>References Valhondo, M., et al.: J. Med. Chem., 56, 7851 (2013); Nichols, D., et al.: Chem. Rev., 108, 1614 (2008)<br></p>

<p>Applications 1-Chloro-3-fluoro-2-propanol is a component of Gliftor (G410000) which is a rodenticide.<br> Not a dangerous good if item is equal to or less than 1g/ml and there is less than 100g/ml in the package<br>References Menon, K., et al.: J. Biochem. Mol. Toxicol., 15, 47 (2001); Xie, W., et al.: J. Hygiene Res. 31, 316 (2002)<br></p>

<p>Applications Protected, labelled Ambrisentan.<br></p>

<p>Impurity Entecavir EP Impurity D<br>Applications 4’-epi-Entecavir is an epimeric impurity of the antiviral drug Entecavir (E558900).<br></p>

<p>Applications Labelled Iprodione. Fungicide.<br>References Lacroix, L., et al.: Phytiatr.-Phytopharm., 23, 165 (1974), Brenneman, T.B., et al.: Plant Dis., 71, 546 (1987),<br></p>

<p>Applications 2'-O-Methyl-d3 Paclitaxel is a labeled analogue of 2'-O-Methyl Paclitaxel (M326135), a potential cytotoxic agent.<br>References Kant, J., et. al.: Bioorg. med. Chem. Lett., 3, 2471 (1993)<br></p>

<p>Applications Selective pre- and post-emergence herbicide. A restricted use pesticide.<br> Not a dangerous good if item is equal to or less than 1g/ml and there is less than 100g/ml in the package<br>References Bradford, D., et al.: Environ. Sci. Technol., 44, 4609 (2010), Trtic-Petrovic, T., et al.: Anal. Bioanal. Chem., 397, 2233 (2010), Stewart, C., et al.: Weed Biol. Man., 10, 40 (2010),<br></p>

<p>Applications 2,2'-((6,6'-(2,4-Di(pyridin-2-yl)cyclobutane-1,3-diyl)bis(1H-indazole-6,3-diyl))bis(sulfanediyl))bis(N-methylbenzamide) is an impurity of Axitinib (A794650), a tyrosine kinase inhibitor. Axitinib is used in cancer therapy.<br>References Wasser, K., et al.: Eur. Radiol., 13, 80 (2003), Park, J., et al.: Clin. Cancer Res., 8, 1172 (2002), Bergers, G., et al.: J. Clin. Invest., 111, 1287 (2003),<br></p>

<p>Stability Air Sensitive<br>Applications MGK 11 is an insect repellent most commonly used commercially as a mosquito repellent.<br>References Rutledge, L., et. al.: J. Med. Entomol., 20, 506 (1983);Steltenkamp, R., et. al.: Eur. Pat. Appl. 9 pp. Patent (1994) CODEN:EPXXDW;Buescher, M., et. al.: J. Med. Entomol., 19, 176 (1982)<br></p>

<p>Impurity Abacavir EP Impurity C; Abacavir USP Related Compound A<br>Applications Descyclopropyl Abacavir (Abacavir EP Impurity C; Abacavir Related Compound A) is an intermediate of Abacavir (A105000). Abacavir is a carbocyclic 2'-deoxyguanosine nucleoside reverse transcriptase inhibitor and an anti-HIV drug used to treat HIV infection (1). Intracellular enzymes convert Abacavir to its active form, carbovir-triphosphate (CBV-TP), which then selectively inhibits HIV reverse transcriptase by incorporating into viral DNA (2). Abacavir is metabolized in the liver by uridine diphosphate glucuronyltransferase and alcohol dehydrogenase resulting in inactive glucuronide and carboxylate metabolites, respectively.<br>References (1) Jackson, A., et al.: Antivir Ther. 17, 19 (2012) (2) Yuen, G. J., et al.: Clin Pharmacokinet. 47, 351 (2008)<br></p>

<p>Applications Metamizole Magnesium Salt is an analgetic, non-opioid drug used in human and veterinary medicinal treatments.<br>References Jasiecka, A. et al.: Polish J. Vet. Sci., 17, 207 (2014); Rogosch, T. et al.: Bioorg. Med. Chem., 20, 101 (2012);<br></p>

<p>Applications Digoxin O-Tetra-acetate is an intermediate used in the synthesis of (3β,5β,12β)-3-[2-[[6-[(2,5-Dioxo-1-pyrrolidinyl)oxy]-6-oxohexyl]amino]-2-oxoethoxy]-12,14-dihydroxycard-20(22)-enolide (D486968), which is a digoxin (D446575) cross-linking reagent.<br></p>

<p>Applications 3,5-Dibromo-4-hydroxybenzonitrile-2,6-d2 (CAS# 1219798-95-4) is a useful isotopically labeled research compound.<br></p>

<p>Applications Phenobarbital Sodium is a barbital drug that can be used to synthesize antiepileptic pharmaceutical compounds.<br>References An, L., et al.: Faming Zhuanli Shenqing, CN 105250316 A, 20160120 (2016)<br></p>

<p>Stability Hygroscopic<br>Applications Intermedine is an unsaturated monoester pyrrolizidine alkaloid that is extracted from the seeds of Amsinckia intermedia, a tarweed that causes enzootic hepatic cirrhosis in horses and hard liver disease in cattle. Intermedine is also a diastereomer of Lycopsamine (L487525), a pyrrolizidine alkaloid that is found in honey and in comfrey (a topical anti-inflammatory agent used to treat patients with arthritis and gout).<br> Not a dangerous good if item is equal to or less than 1g/ml and there is less than 100g/ml in the package<br>References Culvenor, C., et al.: J. Agr. Food Chem., 29 958 (1981); Janes, D., et al.: Nat. Prod. Comm., 7, 861 (2012); Li, Y. &amp; Stermitz, F.: J. Nat. Prod., 51, 1289 (1988); McCulloch, E.: Am. Vet. Med. Assoc., 96, 5 (1940); Pawar, R., et al.: J. Sep. Sci., 33, 200 (2010)<br></p>

<p>Applications 4-Methyl-1,2,3-Thiadiazole-5-Carboxylic Acid (cas# 18212-21-0) is a useful research chemical.<br></p>

<p>Applications 2-Diethylaminoethyl Hexanoate is a compound found in soybean herbicidal safeners.<br>References Jin, G., et al.: Faming Zhuanli Shenqing, CN 106889062 (2017);<br></p>

<p>Applications Labelled trans-Hydroxy Praziquantel (H952405). The main cis-monohydroxylated metabolite of Praziquantel (P702095).<br>References Buehring, K., et al.: Eur. J. Drug Metab. Pharm., 3, 179 (1978), Moldeus, P., et al.: Methods Enzymol., 52, 60 (1978), Cioli, D., et al.: Pharmacol. Ther., 68, 35 (1995),<br></p>

<p>Applications Pipobroman-D8 is a labelled analogue of Pipobroman (P490602).<br> Not a dangerous good if item is equal to or less than 1g/ml and there is less than 100g/ml in the package<br></p>

<p>Applications Tetrabromobisphenol S Dimethyl Ether-d6 is the isotope labelled analog of Tetrabromobisphenol S Dimethyl Ether (T291115); a useful insecticide against house flies and sugar beet aphids. Also found in coating mixtures used for fireproofing of polyester fibers.<br>References Pisanenko, D. A., et al.: Vestn. Kievskogo Politekhnicheskogo Instituta Khimicheskoe Mashinostroenie i Tekhnologiya, 25, 79 (1988); Tomita, M., et al. Fireproofing of polyester fibers and their blends. Jpn. Kokai Tokkyo Koho. JP 54006996 A 19790119. Jan 19, 1979<br></p>

<p>Applications Pyr-Gln-OHis a dipeptide that is found in fruits, has a role as a human metabolite.<br>References Dallmann, Robert. et al., P. NATL. ACAD. SCI. USA. 109, 2625-2629(2012);<br></p>

<p>Applications Estradiol Acetate-d3 is the labelled version of estradiol acetate(H454140); a reactant in the preparation of a modifier conjugate through a physiologically cleavable bond for enhanced drug transport across membranes.<br>References Hale, R., et al.: PCT Int. Appl. (1993), WO 9325197 A1 19931223.<br></p>

<p>Applications 2-Bromoethyl Benzoate-d4 is a labelled analogue of 2-Bromoethyl Benzoate (B810050), a compound used as a reactant in the coupling of challenging heteroaryl halides with alkyl halides via nickel-ctalyzed cross-electrophile coupling.<br>References Hansen, E. C., et al.: J. Org. Chem., 82, 7085 (2017);<br></p>

<p>Applications (R)-8-Hydroxy-3-methyl-1,2,3,4-tetrahydrobenz[a]anthracene-7,12-dione (cas# 681001-30-9) is a compound useful in organic synthesis.<br></p>

<p>Applications 5-(N,N-Diethylcarboxamide)-1-phenylpyridin-2(1H)-one (cas# 1076199-97-7) is a compound useful in organic synthesis.<br></p>

<p>Applications 1,1'-[Dithiobis(methylene)]biscyclopropaneacetic Acid is an intermediate in the synthesis of Montelukast (M568000), a selective leukotriene D4-receptor antagonist used as an antiasthmatic agent.<br></p>

<p>Applications Phorate Sulfone is a metabolite of Phorate (85%, P353500) which is a non-biocumulative organophosphate used as an insecticide and acaricide. Phorate is an inhibitor of acetylcholinesterase and pseudocholinesterase.<br> Not a dangerous good if item is equal to or less than 1g/ml and there is less than 100g/ml in the package<br>References Pandey, G.C. et al.: Ind. J. Comp. Anim. Physiol., 6, 1 (1988); Henderson, M.C. et al.: Biochem. Pharmacol., 68, 959 (2004); Peter, J.V. et al.: NeuroToxicology, 29, 335 (2008);<br></p>

<p>Applications Norapomorphine Glucuronidate is a metabolite of Amomorphine (A727500). Amomorphine is a dopamine (D1 and D2) receptor agonist. Emetic. Antiparkinsonian.<br>References Neumeyer, J.L., et al.: J. Pharm. Sci., 59, 1850 (1970), Ginos, J.Z., et al.: J. Med. Chem., 18, 1194 (1975), Muhtadi, F.J., et al.: Anal. Profiles Drug Subs., 20, 121 (1991),<br></p>

<p>Applications Phorate Oxon Sulfoxide is a major metabolite of Phorate (P353500), an inhibitor of acetylcholinesterase and pseudocholinesterase.<br> Not a dangerous good if item is equal to or less than 1g/ml and there is less than 100g/ml in the package<br>References Boshoff, P.R., et al.: J. Agr. Food Chem., 27, 626 (1979),<br></p>

<p>Applications (S)-Benzylphenobarbital is a derivative of Phenobarbital (P316760), which is an Anticonvulsant; sedative; hypnotic.<br>References Goldenthal, E.I., et al.: Toxicol. Appl. Pharmacol., 18, 185 (1971), Chao, M.K.C., et al.: Anal. Profiles Drug Subs., 7, 359 (1978),<br></p>

<p>Applications N-tert-Butyl-3-isopropyl-5-oxo-4,5-dihydro-1H-1,2,4-triazole-1-carboxamide is a metabolite of Amicarbazone (A605040); a triazolinone herbicide with a broad spectrum of weed control.<br>References Dayan, F., et al.: Weed Science, 57, 579 (2009); Elmore, M., et al.: Weed Technol., 27, 596 (2013); Dong, M., et al.: J. Sep. Sci., 38, 2245 (2015)<br></p>

<p>Applications 13-O-Methylamphotericin B is an antifungal. 13-O-Methylamphotericin B is a derivative of Amphotericin B (A634250), a polypeptide antibiotic active against gram positive bacteria. Antifungal.<br>References Taylor, A.W., et. al.: J. Antibiot., 46, 486 (1993); Asher, I.M., et al.: Anal. Profiles Drug Subs., 6, 1, (1977)<br></p>

<p>Applications Labelled Olmesartan Medoxomil (O550000). Olmesartan Medoxomil is an angiotensin II receptor antagonist. Olmesartan Medoxomil is used as an anti-hypertensive.<br>References Yanagisawa, H., et al.: J. Med. Chem., 39, 323 (1996), Puchler, K., et al.: J. Hypertens., 15, 1809 (1997),<br></p>

<p>Applications Atazanavir-8-(N-methoxycarbonyl)-L-tert-leucine Ester is an impurity of the drug Atazanavir (A790051). Atazanavir is a novel azapeptide HIV protease inhibitor (PI). Antiviral. Like other antiretrovirals, it is used to treat infection of human immunodeficiency virus (HIV). Newer research has been investigating the potential anticancer effects of atazanavir<br>References Palella, F.J. Jr., et al.: N. Engl. J. Med., 338(13), 853 (1998), Nolan, D., et al.: Drugs, 63(23), 2555 (2003), Musial, B.L., et al.: Am. J. Health Syst. Pharm., 61, 1365 (2004), Wood, R., et al.: J. Acquir. Immune Defic. Syndr., 36, 684 (2004),<br></p>

<p>Applications N2-Acetyl Acyclovir Benzoate-d5 is the isotope labelled analog of N2-Acetyl Acyclovir Benzoate (A167975); a derivative of Acyclovir (A192400) which is an orally active acyclic nucleoside with inhibitory activity towards several herpes viruses. Also an antiviral.<br>References Collins, P., et al.: J. Antimicrob. Chemother., 5, 431 (1979); Matsumoto, H., et al.: Chem. Pharm. Bull., 36, 1153 (1988); Whitley, R.J., et al.: N. Engl. J. Med., 327, 782 (1992); Ashton, D.S., et al.: J. Chromatogr. A, 707, 367 (1995)<br></p>