['PHILIP', 'MORRIS', 'U.S.', 'A.', 'INTER-OFFICE', 'CORRESPONDENCE', 'Richmond,', 'Virginia', 'To:', 'Richard', 'Carchman', 'and', 'Cathy', 'Ellis', 'Date:', 'April', '18,', '1990', 'From:', 'J.', 'I.', 'Seeman', 'and', 'R.', 'R.', 'Izac', 'Subject:', 'Determination', 'of', 'Percent', 'Nicotine', 'Racemization', 'During', 'the', 'Smoking', 'Process', 'Recently,', 'you', 'requested', 'that', 'one', 'of', 'us', '(JIS):', 'propose', 'a', 'set', 'of', 'experiments', 'which', 'will', 'evaluate', 'if,', 'and', 'to', 'what', 'extent,', 'nicotine', 'racemizes', 'during', 'the', 'smoking', 'process.', 'As', 'you', 'know,', 'nicotine', 'exists', 'as', 'the', 'optically', 'pure', '($)-(-)-enantiomer', 'in', 'Nicotiana', 'tabacum.', 'There', 'have', 'been', 'a', 'number', 'of', 'conflicting', 'literature', 'reports', 'over', 'the', 'years,', 'some', 'stating', 'that', 'nicotine', 'partially', 'racemizes', 'during', 'the', 'smoking', 'PEOGESS"', 'and', 'another', 'reporting', 'that', 'nicotine', 'does', 'not', 'racemize', 'during', 'this', 'process.?', 'A', '1988', 'PM', 'memo', 'issued', 'by', 'one', 'of', 'us', '(RRI)', 'iidinabes', 'that', 'nicotine', 'in', 'ART', 'cigarettes', 'is', 'partially', 'racemized', 'upon', 'smoking.’', 'In', 'addition,', 'there', 'have', 'been', 'published', 'reports', 'of', 'TACERL', 'EAE', 'TOR', 'Ol', 'nicotine', 'by', 'thermal', 'treatment,', 'typically', 'in', 'the', 'presence', 'of', 'acid', 'or', 'base.', 'As', 'we', 'have', 'discussed,', 'there', 'are', 'many', 'experimental', 'difficulties', 'with', 'determining', 'unambiguously', 'whether', 'or', 'not', 'nicotine', '(partially)', 'racemizes', 'either', 'during', 'the', 'smoking', 'process', 'or', 'under', 'pyrolysis', 'conditions.', 'These', 'include:', '1.', 'The', 'requirement', 'that', 'the', 'nicotine', 'be', 'chemically', 'pure', 'prior', 'to', 'its', 'enantiomeric', 'excess', '(ee)', 'being', 'determined.', '2.', 'To', 'date,', 'polarimetry', 'is', 'the', 'only', 'analytical', 'technique', 'which', 'can', 'effectively', 'analyze', 'the', 'ee', 'of', 'nicotine.', '3.', 'To', 'complicate', 'matters,', 'the', 'optical', 'rotation', 'of', 'nicotine', 'is', 'known', 'to', 'be', 'solvent', 'and', 'concentration', 'dependent.*', 'Also,', 'to', 'rigorously', 'determine', 'ee,', 'one', 'must', 'be', 'certain', 'that', 'there', 'are', 'no', 'contaminants,', 'especially', 'ones', 'having', 'a', 'high', 'rotatory', 'strength.', '4.', 'There', 'is', 'evidence', 'in', 'the', 'literature', 'that', 'a', 'partially', 'racemized', 'nicotine', 'solution', 'can', '"self', 'resolve"', 'during', 'chromatography.*', 'Should', 'such', 'a', 'process', 'occur,', 'the', 'ee', 'obtained', 'would', 'be', 'larger', 'for', 'the', 'sample', 'measured', 'than', 'for', 'the', 'nicotine', 'resulting', 'from', 'the', 'smoking', 'process.', 'Polymer', 'Laboratories', 'Inc.,', 'Amherst,', 'Massachusetts,', 'is', 'now', 'marketing', 'an', 'HPLC', 'on-line', 'detector', 'of', 'optical', 'activity,', 'called', 'a', '"ChiraMonitor."', 'In', 'the', 'promotional', 'literature,', 'this', 'device', 'has', 'been', 'used', 'to', 'determine', 'the', 'ee', 'of', 'nicotine', 'solutions', '(in', 'collaboration', 'with', 'Dr.', 'T.', 'Perfetti', 'of', 'R.', 'J.', 'Reynolds).', 'According', 'to', 'the', 'literature', 'available,', 'the', 'ChiraMonitor', 'is', 'able', 'to', 'detect', '"a', 'difference', 'of', 'about', '0.5%', 'in', 'enantiomeric', 'purity', '(corresponding', 'to', 'a', '1%', 'enantiomeric', 'excess).', 'The', 'literature', 'also', 'indicates', 'that', 'the', 'instrument', 'is', 'very', 'sensitive,', 'i.e.,', '"the', 'mobile', 'phase', 'must', 'be', 'degassed', 'and', 'left', 'under', 'a', 'positive', 'pressure', 'of', 'helium,"', '"sonication', 'of', 'samples', 'prior', 'to', '6PP9E8beoe']