Analysis of local anaesthetics

  • G. T. Tucker
  • M. S. Lennard


Modern regional anaesthesia is practised with a relatively small armamentarium of agents. These can be divided into esters of the procaine type and amides of the lignocaine type; their chemical structures are shown in Table 7.1. Of the compounds. listed, bupivacaine and lignocaine are currently the most widely used in anaesthetic practice. The former is especially popular for providing epidural analgesia during labour and vaginal delivery, owing to its relatively long duration of action and an ability to produce a marked differential blockade favouring sensory rather than motor loss. Etidocaine is a new, long-acting analogue but a tendency to produce a differential motor block largely confines its use to surgical anaesthesia. Prilocaine has fallen out of favour for epidural anaesthesia because of methaemoglobinaemia associated with high doses, although a relatively low propensity for central-nervous-system toxicity commends it for peripheral nerve blocks and intravenous regional anaesthesia. Like lignocaine it is widely used in dentistry.


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  1. Abernathy, D. R., Greenblatt, D. J., and Ochs, H. R. (1982). Lidocaine determination in human plasma with application to single low-dose pharmacokinetic studies. J. Chromatogr. 232, 180–5.CrossRefGoogle Scholar
  2. Adams, R. F., Vandenmark, F. L., and Schmidt, G. (1976). The simultaneous determination of lidocaine and procainamide in serum by use of high-pressure liquid chromatography. Clin. Chim. Acta 69, 515–24.PubMedCrossRefGoogle Scholar
  3. Adjepon-Yamoah, K. K., and Prescott, L. F. (1974). Gas-liquid chromatographic estimation of lignocaine, ethylglycylxylidide, glycylxylidide and 4-hydroxy xylidine in plasma and urine. J. Pharm. Pharmac. 26, 889–93.CrossRefGoogle Scholar
  4. Ahmad, K., and Medzihradsky, F. (1971). Distribution of lidocaine in blood and tissues after single doses and steady infusion. Res. Comm. Chem. Path. Pharmac. 2, 813–28.Google Scholar
  5. Alkalay, D., Carlsen, S., and Wagner, W. E. (1981). Quantitation of the local anesthetic dibucaine with gas chromatography/mass spectrometry. Analyt. Lett. 14, 1745–56.CrossRefGoogle Scholar
  6. Ambre, J. J., Ruo, T.-I., Smith, G. L., Backes, D., and Smith, C. M. (1982). Ecgonine methyl ester, a major metabolite of cocaine. J. Analyt. Toxicol. 6, 26–9.CrossRefGoogle Scholar
  7. Asling, J. H., Shnider, S. M., Wilkinson, G. R., and Way, E. L. (1969). Gas chromatographic determination of mepivacaine in capillary blood. Anesthesiology 31, 458–61.CrossRefGoogle Scholar
  8. Barnett, G., Hawks, R., and Resnick, R. (1981). Cocaine pharmacokinetics in humans. J. Ethnopharmac. 3, 353–66.CrossRefGoogle Scholar
  9. Beckett, A. H., Boyes, R. N., and Appleton, P. J. (1966). The metabolism and excretion of lignocaine in man. J. Pharm. Pharmac. 18 (suppl.), 76–81S.CrossRefGoogle Scholar
  10. Beckett, A. H., Boyes, R. N., and Parker, J. B. R. (1965). Determination of lignocaine in blood and urine in human subjects undergoing local analgesic procedures. Anaesthesia 20, 294–8.CrossRefGoogle Scholar
  11. Benowitz, N., and Rowland, M. (1973). Determination of lidocaine in blood and tissues. Anesthesiology 39, 639–41.PubMedCrossRefGoogle Scholar
  12. Berlin, A., Persson, B.-A., and Belfrage, P. (1973). Micromethod for the determination of bupivacaine in maternal and foetal blood during obstetric analgesia. J. Pharm. Pharmac. 25, 466–9.CrossRefGoogle Scholar
  13. Blankenbaker, W. L., Di Fazio, C. A., and Berry, F. A. (1975). Lidocaine and its metabolites in the newborn. Anesthesiology 42, 325–30.PubMedCrossRefGoogle Scholar
  14. Bouche, R., and Minetti, R. (1974). Quantitative micro-determination of 2,6-pipecolylxylidide by gas-liquid chromatography. J. Chromatogr. 90, 191–4.PubMedCrossRefGoogle Scholar
  15. Boyes, R. N. (1975). A review of the metabolism of amide local anaesthetics. Br. J. Anaesth. 38, suppl., 225–30.Google Scholar
  16. Braid, D. P., and Scott, D. B. (1965). The systemic absorption of local analgesic drugs. Ibid. 37, 394–404.PubMedCrossRefGoogle Scholar
  17. Breuer, H. (1982). Gas-liquid chromatographic determination of lidocaine in cat plasma using mepivacaine as internal standard. J. Chromatogr. 231, 65–72.PubMedCrossRefGoogle Scholar
  18. Bridenbaugh, P. O., Tucker, G. T., Moore, D. C., Bridenbaugh, L. D., and Thompson, G. E. (1974). Preliminary clinical evaluation of etidocaine (Duranest): a new long-acting local anesthetic agent. Acta Anaesth. Scand. 18, 165–71.PubMedCrossRefGoogle Scholar
  19. Brodie, B. B., Lief, P. A., and Poet, R. (1948). The fate of procaine in man following its intravenous administration and methods for the estimation of procaine and diethylaminoethanol. J. Pharmac. Exper. Therap. 94, 366–95.Google Scholar
  20. Bromage, P. R., and Robson, J. G. (1961). Concentrations of lignocaine in the blood after intravenous, intramuscular, epidural and endotracheal administration. Anaesthesia 16, 461–78.PubMedCrossRefGoogle Scholar
  21. Budd, R. D. (1981). Cocaine radioimmunoassay-structure versus reactivity. Clin. Toxicol. 18, 773–82.PubMedCrossRefGoogle Scholar
  22. Burm, A. G. L., Van Kleef, J. W., and De Boer, A. G. (1982). Gas chromatographic determination of bupivacaine in plasma using a support coated open tubular column and a nitrogen-selective detector. Anesthesiology 57, 527–9.PubMedCrossRefGoogle Scholar
  23. Caille, G., LeLorier, J., Latour, Y., and Besner, J. G. (1977). GLC determination of lidocaine in human plasma. J. Pharm. Sci. 66, 1383–5.PubMedCrossRefGoogle Scholar
  24. Caldwell, J., Moffatt, J. R., Smith, R. L., Lieberman, B. A., Beard, R. W., Snedden, W., and Wilson, B. W. (1977). Determination of bupivacaine in human fetal and neonatal blood samples by quantitative single ion monitoring. Biomed. Mass Spectrom. 4, 322–5.PubMedCrossRefGoogle Scholar
  25. Calvo, R., Carlos, R., and Erill, S. (1980). Effects of disease and acetazolamide on procaine hydrolysis by red cell enzymes. Clin. Pharmac. Ther. 27, 175–83.CrossRefGoogle Scholar
  26. Cameron, J. D. (1974). The gas chromatographic determination of plasma concentrations of some local anesthetics using a nitrogen detector. Clin. Chim. Acta 56, 307–9.PubMedCrossRefGoogle Scholar
  27. Chinn, D. M., Crouch, D. J., Peat, M. A., Finkle, B. S., and Jennison, T. A. (1980). Gas chromatography-chemical ionization mass spectrometry of cocaine and its metabolites in biological fluids. J. Analyt. Toxicol. 4, 37–42.CrossRefGoogle Scholar
  28. Clarke, E. G. C. (1969). Isolation and Identification of Drugs. Pharmaceutical Press, London.Google Scholar
  29. Cobb, M. E., Buckley, N., Hu, M. W., Miller, J. G., Singh, P., and Schneider, R. S. (1977). Homogeneous enzyme immunoassay for lidocaine in serum. Clin. Chem. 23, 1161.Google Scholar
  30. Cone, E. J., Buchwald, W. F., and Darwin, W. D. (1982). Analytical controls in drug metabolism studies. 2: Artifact formation during chloroform extraction of drugs and metabolites with amine substituents. Drug Metab. Disp. 10, 561–7.Google Scholar
  31. Cousins, M. J., and Bridenbaugh, P. O. (eds) (1980). Neural Blockade in Clinical Anesthesia and Management of Pain. Lippincott, Philadelphia.Google Scholar
  32. Covino, B. G., and Vassallo, H. G. (1976). Local Anesthetics. Mechanisms of Action and Clinical Use. Grune and Stratton, New York.Google Scholar
  33. Dawkins, C. J. M. (1969). An analysis of the complications of extradural and caudal block. Anaesthesia 24, 554–63.PubMedCrossRefGoogle Scholar
  34. De Boer, A. G., Breimer, D. D., Pronk, J., and Gubbens-Stibbe, J. M. (1980). Rectal bioavailability of lidocaine in rats: absence of significant first-pass elimination. J. Pharm. Sci. 69, 804–7.PubMedCrossRefGoogle Scholar
  35. De Gelder, D. J., De Leede, L. G. J., and De Boer, A. G. (1981). Assay of lidocaine and 5 metabolites by capillary gas chromatography. Proc. 41st Int. Congr. Pharmaceutical Sciences, Vienna, abstr. No. 5.Google Scholar
  36. De Jong, R. H. (1977). Local Anesthetics, 2nd ed. Charles C. Thomas, Springfield.Google Scholar
  37. Dennhardt, R., and Konder, H. (1980). Metabolite von bupivacain beim menschen. Regional Anaesth. 3, 25–6.Google Scholar
  38. Desch, G., Cavadore, D., Jullien, Y., Mercier, L., Descomps, B., and De Rodez, M. (1981). Analg. Anesth. Rean. 2, 158–68.Google Scholar
  39. DiFazio, C. A., and Brown, R. E. (1971). The analysis of lidocaine and its postulated metabolites. Anesthesiology 34, 86–8.PubMedCrossRefGoogle Scholar
  40. Dvorchik, B. H., Miller, S. H., and Graham, W. P. (1977). Gas chromatographic determination of cocaine in whole blood and plasma using a nitrogen-sensitive flame ionization detector. J. Chromatogr. 135, 141–8.PubMedCrossRefGoogle Scholar
  41. Edhorn, G. A. (1971). Determination of lidocaine in whole blood by gas chromatography. Canad. Anaesth. Soc. J. 18, 189–97.PubMedCrossRefGoogle Scholar
  42. Evans, M. A., and Moriarty, T. (1980). Analysis of cocaine and cocaine metabolites by high pressure liquid chromatography. J. Analyt. Toxicol. 4, 19–22.CrossRefGoogle Scholar
  43. Fish, F., and Wilson, W. D. C. (1969a). Gas chromatographic determination of morphine and cocaine in urine. J. Chromatogr. 40, 164–8.PubMedCrossRefGoogle Scholar
  44. Fish, F., and Wilson, W. D. C. (1969b). Excretion of cocaine and its metabolites in man. J. Pharm. Pharmac. 21, 135–8S.CrossRefGoogle Scholar
  45. Flanagan, R. J., Storey, G. C. A., Bhamra, R. K., and Jane, I. (1982). High-performance liquid chromatographic analysis of basic drugs on silica columns using non-aqueous ionic eluents. J. Chromatogr. 247, 15–37.CrossRefGoogle Scholar
  46. Fletcher, S. M., and Hancock, V. S. (1981). Potential errors in benzoylecgonine and cocaine anatysis. Ibid. 206, 193–5.PubMedCrossRefGoogle Scholar
  47. Foldes, F. F., Davidson, G. N., Duncalf, D., and Kuwabara, S. (1965). The intravenous toxicity of local anesthetic agents in man. Clin. Pharmac. Ther. 6, 328–35.CrossRefGoogle Scholar
  48. Fukuda, J., and Momose, A. (1975). Determination of tetracaine N-oxide in urine by gas chromatography. Yakugaku Zasshi 95, 480–83.PubMedGoogle Scholar
  49. Gal, J., Freedman, M. D., Kumar, E., and Freed, C. R. (1981). A rapid and simple microassay for lidocaine in human blood plasma using gas-liquid chromatography with nitrogen detection. Therap. Drug Monit. 3, 177–80.CrossRefGoogle Scholar
  50. Garland, W. A., Trager, W. F., and Nelson, S. D. (1974). Direct (non-chromatographic) quantification of drugs and their metabolites from human plasma utilizing chemical ionization mass spectrometry and stable isotope labeling: quinidine and lidocaine. Biomed. Mass Spectrom. 1, 124–9.PubMedCrossRefGoogle Scholar
  51. Goehl, T. J., Davenport, J. B., and Stanley, M. J. (1973). Distribution, biotransformation and excretion of bupivacaine in the rat and the monkey. Xenobiotica 3, 761–72.PubMedCrossRefGoogle Scholar
  52. Goto, S., and Itano, T. (1979). Hydrolysis of lidocaine and its metabolites. Yakugaku Zasshi 99, 146–54.PubMedGoogle Scholar
  53. Graffeo, A. P., Lin, D. C. K., and Foltz, R. L. (1976). Analysis of benzoylecgonine in urine by high-performance liquid chromatography and gas chromatography-mass spectrometry. J. Chromatogr. 126, 717–22.PubMedCrossRefGoogle Scholar
  54. Green, R. L., Lewis, J. E., Kraus, S. J., and Frederickson, E. L. (1974). Elevated plasma procaine concentrations after administration of procaine penicillin G. New Engl. J. Med. 291, 223–6.PubMedCrossRefGoogle Scholar
  55. Halkin, H., Meffin, P., Melmon, K. L., and Rowland, M. (1975). Influence of congestive heart failure on blood levels of lidocaine and its active monodeethylated metabolite. Clin. Pharmac. Ther. 17, 669–76.CrossRefGoogle Scholar
  56. Hawkins, J. D., Bridges, R. R., and Jennison, T. A. (1982). A single-step assay for lidocaine and its major metabolite, monoethylglycinexylidide, in plasma by gas-liquid chromatography and nitrogen phosphorus detection. Therap. Drug Monit. 4, 103–106.CrossRefGoogle Scholar
  57. Hawks, R. L., Kopin, I. J., Colburn, R. W., and Thoa, N. B. (1974). Norcocaine: a pharmacologically active metabolite of cocaine found in brain. Life Sci. 15, 2189–95.PubMedCrossRefGoogle Scholar
  58. Heath, M. L. (1982). Deaths after intravenous regional anaesthesia. Br. Med. J. 2, 913–4.CrossRefGoogle Scholar
  59. Hignite, C. E., Tschanz, C., Steiner, J., Huffman, D. H., and Azarnoff, D. L. (1978). Quantitation of lidocaine and its deethylated metabolites in plasma and urine by gas chromatography-mass fragmentography. J. Chromatogr. 161, 243–9.PubMedCrossRefGoogle Scholar
  60. Hill, J., Roussin, A., LeLorier, J., and Caille, G. (1980). High-pressure liquid chromatographic determination of lidocaine and its active deethylated metabolites. J. Pharm. Sci. 69, 1341–3.PubMedCrossRefGoogle Scholar
  61. Holt, D. W., Flanagan, R. J., Hayler, A. M., and Loizou, M. (1979a). Simple gas-liquid chromatographic method for the measurement of mexiletine and lignocaine in bloodplasma or serum. J. Chromatogr. 169, 295–301.PubMedCrossRefGoogle Scholar
  62. Holt, D. W., Loizou, M., and Wyse, R. K. (1979b). Gas-liquid chromatographic measurement of lignocaine in small samples of canine myocardium after enzymatic digestion. J. Clin. Pathol. 32, 225–8.PubMedPubMedCentralCrossRefGoogle Scholar
  63. Hucker, H. B., and Stauffer, S. C. (1976). GLC analysis of lidocaine in plasma using a novel nitrogen-sensitive detector. J. Pharm. Sci. 65, 926–7.PubMedCrossRefGoogle Scholar
  64. Irgens, T. R., Henderson, W. M., and Shelver, W. H. (1976). GLC analysis of lidocaine in blood using an alkaline flame-ionization detector. Ibid. 65, 608–610.PubMedCrossRefGoogle Scholar
  65. Ishikawa, T. (1974). Determination of local anesthetics in the blood and cerebrospinal fluid by gas chromatography. Jap. J. Anesthesiol. 23, 246–50.Google Scholar
  66. Jain, S., and Johnston, A. (1979). The measurement of lignocaine at low concentrations in plasma, a comparison of gas liquid chromatography with enzyme immunoassay. Br. J. Clin. Pharmac. 8, 598–9.CrossRefGoogle Scholar
  67. Jatlow, P. I., and Bailey, D. N. (1975). Gas-chromatographic analysis for cocaine in human plasma, with use of a nitrogen detector. Clin. Chem. 21, 1918–21.PubMedGoogle Scholar
  68. Jatlow, P. I., Van Dyke, C., Barash, P., and Byck, R. (1978). Measurement of benzoylecgonine and cocaine in urine, separation of various cocaine metabolites using reversedphase high-performance liquid chromatography. J. Chromatogr. 152, 115–21.PubMedCrossRefGoogle Scholar
  69. Javaid, J. I., Dekirmenjian, H., Davis, J. M., and Schuster, C. R. (1978). Determination of cocaine in human urine, plasma and red blood cells by gas-liquid chromatography. Ibid. 152, 105–13.PubMedCrossRefGoogle Scholar
  70. Jindal, S. P., and Vestergaard, P. (1978). Quantitation of cocaine and its principal metabolite, benzoylecgonine, by GLC-mass spectrometry using stable isotope labeled analogs as internal standards. J. Pharrn Sci. 67, 811–4.CrossRefGoogle Scholar
  71. Jindal, S. P., Lutz, T., and Vestergaard, P. (1978). Mass spectrometric determination of cocaine and its biologically active metabolite, norcocaine, in human urine. Biomed. Mass Spectrom. 5, 658–63.PubMedCrossRefGoogle Scholar
  72. Kacprowicz, A. T. (1982). Improved gas-chromatographic determination of lignocaine in plasma. Clin. Chem. 28, 545–6.PubMedGoogle Scholar
  73. Karch, F. E., and Chmielewski, K. F. (1981). GLC assay for lidocaine in human plasma. J. Pharm. Sci. 70, 229–30.PubMedCrossRefGoogle Scholar
  74. Kaul, B., Millian, S. J., and Davidow, B. (1976). The development of a radioimmunoassay for detection of cocaine metabolites. J. Pharmac. Exper. Ther. 199, 171–8.Google Scholar
  75. Keenaghan, J. B. (1968). The determination of lidocaine and prilocaine in whole blood by gas chromatography. Anesthesiology 29, 110–2.PubMedCrossRefGoogle Scholar
  76. Keenaghan, J. B., and Boyes, R. N. (1972). The tissue distribution, metabolism and excretion of lidocaine in rats, guinea pigs, dogs and man. J. Pharmac. Exper. Ther. 180, 454–63.Google Scholar
  77. Kline, B. J., and Martin, M. F. (1978). Simplified GLC assay for lidocaine in plasma. J. Pharm. Sci. 67, 887–8.PubMedCrossRefGoogle Scholar
  78. Kogan, M. J., Verebey, K. G., DePace, A. C., Resnick, R. B., and Mulé, S. J. (1977). Quantitative determination of benzoylecgonine and cocaine in human biofluids by gas-liquid chromatography. Analyt. Chem. 49, 1965–9.CrossRefGoogle Scholar
  79. Krogh, K., and Jellum, E. (1981). Urinary metabolites of chloroprocaine studied by combined gas chromatography-mass spectrometry. Anesthesiology 54, 329–32.CrossRefGoogle Scholar
  80. Krogh, K., and Jellum, E. (1982). Urinary metabolites of chloroprocaine. Ibid. 56, 483–4.CrossRefGoogle Scholar
  81. Kruczek, M. E. (1981). A rapid gas-liquid chromatographic determination of serum lidocaine using a nitrogen-phosphorus specific detector. J. Pharmac. Methods. 5, 137–41.CrossRefGoogle Scholar
  82. Kuhnert, B. R., Kuhnert, P. M., and Reese, A. L. P. (1981a). Measurements of 2-chloro-2-chloroprocaine in obstetric patients and their neonates after epidural anesthesia. Anesthesiology 53, 21–5.CrossRefGoogle Scholar
  83. Kuhnert, B. R., Kuhnert, P. M., and Reese, A. L. P. (1981a). Measurements of 2-chloroprocaine in plasma by selected ion monitoring. J. Chromatogr. 224, 488–91.CrossRefGoogle Scholar
  84. Kuhnert, B. R., Kuhnert, P. M., and Reese, A. L. P. (1982). Urinary metabolites of chloroprocaine. Anaesthesiology 56, 483.CrossRefGoogle Scholar
  85. Kuhnert, P. M., Kuhnert, B. R., Stitts, J. M., and Gross, T. L. (1981b). The use of a selected ion monitoring technique to study the disposition of bupivacaine in mother, fetus and neonate following epidural anesthesia for Cesarian section ibid. 55, 611–17.CrossRefGoogle Scholar
  86. Lagerstrom, P.-O., and Persson, B.-A. (1978). Liquid chromatography in the monitoring of plasma levels of antiarrhythmic drugs. J. Chromatogr. 149, 331–40.PubMedCrossRefGoogle Scholar
  87. Lee, K. Y., Nurok, D., Zlatkis, A., and Karmen, A. (1978). Simultaneous determination of antiarrhythmia drugs by high-performance thin-layer chromatography. Ibid. 158, 403–10.PubMedCrossRefGoogle Scholar
  88. Lehane, D. P., Wissert, P. J., Menyharth, P., Levy, A. L., and Kukucka, A. (1979). Enzyme immunoassay for serum lidocaine in antiarrhythmic therapy. Clin. Chem. 25, 614–16.PubMedGoogle Scholar
  89. Lesko, L. J., Ericson, J., Ostheimer, G., and Marion, A. (1980). Simultaneous determination of bupivacaine and 2,6-pipecoloxylidide in serum by gas-liquid chromatography. J. Chromatogr. 182, 226–31.PubMedCrossRefGoogle Scholar
  90. Liu, Y., Budd, R. D., and Griesemer, E. C. (1982). Study of the stability of cocaine and benzoylecgonine, its major metabolite, in blood samples. Ibid. 248, 318–20.PubMedCrossRefGoogle Scholar
  91. Lurie, A. O., and Weiss, J. B. (1970). Blood concentration of mepivacaine and lidocaine in mother and baby after epidural anesthesia. Amer. J. Obstet. Gynecol. 106, 850–6.CrossRefGoogle Scholar
  92. Maes, R., Kananen, G., and Sunshine, I. (1969). Determination of mepivacaine in blood and urine. Anesthesiology 30, 657–9.PubMedCrossRefGoogle Scholar
  93. Masoud, A. N., and Krupski, D. M. (1980). High-performance liquid chromatographic analysis of cocaine in human plasma. J. Analyt. Toxicol. 4, 305–10.CrossRefGoogle Scholar
  94. Masoud, A. N., Scratchley, G. A., Stohs, S. J., and Wingard, D. W. (1978). Simultaneous determination of lidocaine (lignocaine) and thiopental in plasma using high pressureliquid chromatography. J. Liq. Chromatog. 1, 607–16.CrossRefGoogle Scholar
  95. Mather, L. E., and Cousins, M. J. (1979). Local anaesthetics and their current clinical use. Drugs 18, 185–205.PubMedCrossRefGoogle Scholar
  96. Mather, L. E., and Tucker, G. T. (1974). Meperidine and other basic drugs: General method for their determination in plasma. J. Pharm. Sci. 63, 306–7.PubMedCrossRefGoogle Scholar
  97. McCurdy, H. H. (1980). Quantitation of cocaine and benzoylecgonine after Jetube extraction and derivatization. J. Analyt. Toxicol. 4, 82–5.CrossRefGoogle Scholar
  98. Medzihradsky, F., and Dahlstrom, P. J. (1975). Concurrent determination of narcotic drugs in plasma by gas-liquid chromatography. Pharmac. Res. Commun. 7, 55–69.CrossRefGoogle Scholar
  99. Mihaly, G. W., Moore, R. G., Thomas, J., Triggs, E. J., Thomas, D., and Shanks, C. A. (1978). The pharmacokinetics and metabolism of the anilide local anaesthetics in neonates. 1: Lignocaine. Eur. J. Clin. Pharmac. 13, 143–52.CrossRefGoogle Scholar
  100. Miller, E., Walberg, C., and Haywood, L. J. (1981). Rapid assessment of lidocaine in cardiac patients by enzyme immunoassay. Ther. Drug Monit. 3, 85–9.PubMedCrossRefGoogle Scholar
  101. Momose, A., and Fukuda, J. (1976). A new metabolite of tetracaine. Chem. Pharm. Bull. 24, 1637–40.PubMedCrossRefGoogle Scholar
  102. Morgan, D. J., Cousins, M. J., McQuillan, D., and Thomas, J. (1977). Disposition and placental transfer of etidocaine in pregnancy. Eur. J. Clin. Pharmac. 12, 359–365.CrossRefGoogle Scholar
  103. Mulé, S. J., Jukofsky, D., Kogan, M., De Pace, A., and Verebey, K. (1977). Evaluation of the radioimmunoassay for benzoylecgonine (a cocaine metabolite) in human urine. Clin. Chem. 23, 796–801.PubMedGoogle Scholar
  104. Naito, E., Matsuki, M., and Shimoji, K. (1977). A simple method for gas chromatographic determination of lidocaine in tissues. Anesthesiology 47, 466–7.PubMedCrossRefGoogle Scholar
  105. Narang, P. K., Crouthamel, W. G., Carliner, N. H., and Fisher, M. L. (1978). Lidocaine and its active metabolites. Clin. Pharmac. Ther. 24, 654–62.CrossRefGoogle Scholar
  106. Nation, R. L., Triggs, E. J., and Selig, M. (1976). Gas chromatographic method for the quantitative determination of lidocaine and its metabolite monoethylglycinexylidide in plasma. J. Chromatogr. 116, 188–93.PubMedCrossRefGoogle Scholar
  107. Nation, R. L., Peng, G. W., and Chiou, W. L. (1979). High-performance liquid chromatographic method for the simultaneous determination of lidocaine and its N-dealkylated metabolites in plasma. Ibid. 162, 466–73.PubMedCrossRefGoogle Scholar
  108. Nayak, P. K., Misra, A. Z., and Mulé, S. J. (1976). Physiological disposition and biotransformation of 3H-cocaine in acutely and chronically treated rats. J. Pharmac. Exper. Ther. 196, 556–69.Google Scholar
  109. Nelson, S. D., Garland, W. A., Breck, G. D., and Trager, W. F. (1977). Quantification of lidocaine and several metabolites utilizing chemical-ionization mass spectrometry and stable isotope labeling. J. Pharm. Sci. 66, 1180–90.PubMedCrossRefGoogle Scholar
  110. O’Brien, J. E., Abbey, V., Hinsvark, O., Perel, J., and Finster, M. (1979). Metabolism and measurement of chloroprocaine, an ester-type local anesthetic. Ibid. 68, 75–8.PubMedCrossRefGoogle Scholar
  111. Pape, B. E. (1981). Antibody selectivity of a quantitative immunochemical assay for serum lidocaine. Clin. Chem. 27, 2032–4.PubMedGoogle Scholar
  112. Pape, B. E., Whiting, R., Parker, K. M., and Mitra, R. (1978). Enzyme immunoassay and gas-liquid chromatography compared for determination of lidocaine in serum. Ibid. 24, 2020–2.PubMedGoogle Scholar
  113. Park, G. B., Erdtmansky, P. E., Brown, R. R., Kullberg, M. P., and Edelson, J. (1980). Analysis of mepivacaine, bupivacaine, etidocaine, lidocaine and tetracaine. J. Pharm. Sci. 69, 603–5.PubMedCrossRefGoogle Scholar
  114. Pfeifer, H. J., Greenblatt, D. J., and Koch-Weser, J. (1976). Clinical use and toxicity of intravenous lidocaine. A report from the Boston Collaborative Drug Surveillance Program. Amer. Heart. J. 92, 168–73.PubMedCrossRefGoogle Scholar
  115. Pratt, E. L., Warrington, H. L., and Greco, J. (1967). The gas chromatographic determination of mepivacaine in blood with a note on other local anesthetics. Anesthesiology 28, 432–7.PubMedCrossRefGoogle Scholar
  116. Rauckman, E. J., Rosen, G. M., and Cavagnaro, J. (1982). Norcocaine nitroxide. A potential hepatotoxic metabolite of cocaine. Mol. Pharmac. 21, 458–63.Google Scholar
  117. Reynolds, F. (1971). Metabolism and excretion of bupivacaine in man. A comparison with mepivacaine. Br. J. Anaesth. 43, 33–37.PubMedCrossRefGoogle Scholar
  118. Reynolds, F., and Beckett, A. H. (1968). The determination of bupivacaine, lignocaine and mepivacaine in human blood. J. Pharm. Pharmac. 20, 704–8.CrossRefGoogle Scholar
  119. Rosseel, M. T., and Bogaert, M. G. (1978). Determination of lidocaine and its desethylated metabolites in plasma by capillary column gas-liquid chromatography. J. Chromatogr. 154, 99–102.PubMedCrossRefGoogle Scholar
  120. Rowland, M., Thomson, P. D., Guichard, A., and Melmon, K. L. (1971). Disposition kinetics of lidocaine in normal subjects. Ann. New York Acad. Sci. 179, 383–98.CrossRefGoogle Scholar
  121. Seifen, A. B., Ferrari, A. A., Seifen, E. E., Thompson, D. S., and Chapman, J. (1979). Pharmacokinetics of intravenous procaine infusion in humans. Anesth. Analg. 58, 382–6.PubMedCrossRefGoogle Scholar
  122. Smith, R. H., Brewster, M. A., MacDonald, J. A., and Thompson, D. S. (1978). Measurement of chloroprocaine and procaine in plasma by flame ionization gas-liquid chromatography. Clin. Chem. 24, 1599–1602.PubMedGoogle Scholar
  123. Spechtmeyer, H., and Steinbach, H. (1969). Gaschromatographische bestimmung einiger lokalanasthetica und ihrer alkylamino-metabolite in biologischem material. Arzneim. Forsch 19, 1754–6.Google Scholar
  124. Stargel, W. W., Roe, C. R., Routledge, P. A., and Shand, D. G. (1979). Importance of blood-collection tubes in plasma lidocaine determinations. Clin. Chem. 25, 617–9.PubMedGoogle Scholar
  125. Stewart, D. J., Inaba, T., Lucassen, M., and Kalow, W. (1979). Cocaine metabolism: Cocaine and norcocaine hydrolysis by liver and serum esterases. Clin. Pharmac. Ther. 25, 464–8.CrossRefGoogle Scholar
  126. Stewart, D. J., Inaba, T., Tang, B. K., and Kalow, W. (1977). Hydrolysis of cocaine in human plasma by cholinesterase. Life. Sci. 20, 1557–64.PubMedCrossRefGoogle Scholar
  127. Strong, J. M., and Atkinson, A. J. (1972). Simultaneous measurement of plasma concentrations of lidocaine and its desethylated metabolite by mass fragmentography. Analyt. Chem. 44, 2287–90.CrossRefGoogle Scholar
  128. Strong, J. M., Mayfield, D. E., Atkinson, A. J., Burris, B. C., Raymon, F., and Webster, L. T. (1975). Pharmacological activity, metabolism and pharmacokinetics of glycinexylidide. Clin. Pharmac. Ther. 17, 184–94.CrossRefGoogle Scholar
  129. Sung, C. Y., and Truant, A. P. (1954). The physiological disposition of lidocaine and its comparison in some respects with procaine. J. Pharmac. Exper. Ther. 112, 432–43.Google Scholar
  130. Svinhufved, G., Ortengren, B., and Jacobsson, S. E. (1965). The estimation of lidocaine and prilocaine in biological material by gas chromatography. Scand. J. Clin. Lab. Invest. 17, 162–4.CrossRefGoogle Scholar
  131. Thomas, J., and Meffin, P. (1972). Aromatic hydroxylation of lidocaine and mepivacaine in rats and humans. J. Med. Chem. 15, 1046–9.PubMedCrossRefGoogle Scholar
  132. Thomas, J., Climie, C. R., and Mather, L. E. (1968). Placental transfer of lignocaine following lumbar epidural administration. Br. J. Anaesth. 40, 965–71.PubMedCrossRefGoogle Scholar
  133. Thomas, J., Climie, C. R., and Mather, L. E. (1969). The maternal plasma levels and placental transfer of bupivacaine following epidural analgesia. Ibid. 41, 1035–40.PubMedCrossRefGoogle Scholar
  134. Thomas, J., Morgan, D., and Vine, J. (1976). Metabolism of etidocaine in man. Xenobiotica 6, 39–48.PubMedCrossRefGoogle Scholar
  135. Tobin, T., Tai, C. Y., and Arnett, S. (1975). Recovery of procaine from biological fluids. Res. Commun. Chem. Path. Pharmac. 11, 187–94.Google Scholar
  136. Tucker, G. T. (1970). Determination of bupivacaine (Marcaine) and other anilide-type local anesthetics in human blood and plasma by gas chromatography. Anesthesiology, 32, 255–60.PubMedCrossRefGoogle Scholar
  137. Tucker, G. T. (1975). Biotransformation and toxicity of local anaesthetics. Acta Anaesth. Belg. 26 (suppl.), 123–40.Google Scholar
  138. Tucker, G. T. (1983a). Chemistry and pharmacology of local anaesthetic drugs. In Henderson, J. J., and Nimmo, W. S. (eds), Practical Regional Anaesthesia. Blackwell, Oxford.Google Scholar
  139. Tucker, G. T. (1983b). Pharmacokinetics of local anaesthetic drugs. Ibid.Google Scholar
  140. Tucker, G. T., and Mather, L. E. (1979). Clinical pharmacokinetics of local anaesthetics. Clin. Pharmacokin. 4, 241–78.CrossRefGoogle Scholar
  141. Valentour, J. C., Aggarwal, V., McGee, M. P., and Goza, S. W. (1978). Cocaine and benzoylecgonine determinations in postmortem samples by gas chromatography. J. Analyt. Toxicol. 2, 134–7.CrossRefGoogle Scholar
  142. Van Dyke, C., Barash, P. G., Jatlow, P., and Byck, R. (1976). Cocaine: Plasma concentrations after intranasal application in man. Science 191, 859–61.PubMedCrossRefGoogle Scholar
  143. Verheesen, P. E., Brombacher, P. J., Cremers, H. M. H. G., and De Boer, R. (1980). Determination of low levels of bupivacaine (Marcaine) in plasma during epidural analgesia. J. Clin. Chem. Clin. Biochem. 18, 351–3.PubMedGoogle Scholar
  144. Vigouroux, M., Montay, G., Benoit, N., Duckert, L., Roquet, F., and Reynier, M. (1978). Methode de dosage dans le sang de la lidocaine (Xylocaine) et de l’etidocaine (Duranest) par chromatographie en phase gazeuse. Anesth. Analg. Rean. 35, 1045–50.Google Scholar
  145. Vine, J., Morgan, D., and Thomas, J. (1978). The identification of eight hydroxylated metabolites of etidocaine by chemical ionization mass spectrometry. Xenobiotica 8, 509–13.PubMedCrossRefGoogle Scholar
  146. Von Minden, D. L., and d’Amato, N. A. (1977). Simultaneous determination of cocaine and benzoylecgonine in urine by gas-liquid chromatography. Analyt. Chem. 49. 1974–7.CrossRefGoogle Scholar
  147. Walberg, C. B. (1978). Lidocaine by enzyme immunoassay. J. Analyt. Toxicol. 2, 121–3.CrossRefGoogle Scholar
  148. Wallace, J. E., Hamilton, H. E., Schwertner, H., King, D. E., McNay, J. L., and Blum, K. (1975). Thin-layer chromatographic determination of cocaine and benzoylecgonine in urine. J. Chromatogr. 114, 433–41.PubMedCrossRefGoogle Scholar
  149. Wallace, J. E., Hamilton, H. E., King, D. E., Bason, D. J., Schwertner, H. A., and Harris, S. C. (1976). Gas-liquid chromatographic determination of cocaine and benzoylecgonine in urine. Analyt. Chem. 48, 34–8.CrossRefGoogle Scholar
  150. Wilkinson, G. R., and Lund, P. C. (1970). Bupivacaine levels in plasma and cerebrospinal fluid following peridural administration. Anesthesiology 33, 482–6.PubMedCrossRefGoogle Scholar
  151. Wisnicki, J. L., Tong, W. P., and Ludlum, D. B. (1979). Analysis of lidocaine and its dealkylated metabolites by high-pressure liquid chromatography. Clin. Chim. Acta 93, 279–82.PubMedCrossRefGoogle Scholar
  152. Woods, L. A., Cochin, J., Fomefeld, E. J., McMahon, F. G., and Seevers, M. H. (1951). The estimation of amines in biological materials with critical data for cocaine and mescaline. J. Pharmac. Exper. Ther. 101, 188–99.Google Scholar
  153. Zylber-Katz, E., Granit, L., and Leby, M. (1978). Gas-liquid chromatographic determination of bupivacaine and lidocaine in plasma. Clin. Chem. 24, 1573–5.PubMedGoogle Scholar

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  • G. T. Tucker
  • M. S. Lennard

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