Gygi S P, Wilkins D G, Rollins D E
Department of Pharmacology and Toxicology, University of Utah, Salt Lake City 84112, USA.
J Pharm Sci. 1997 Feb;86(2):209-14. doi: 10.1021/js960268h.
Drugs and endogenous compounds circulating in the blood may ultimately become incorporated into a growing hair shaft. Hair analysis for drugs of abuse is a growing field in the area of forensic and clinical toxicology. However, the underlying principles that govern drug incorporation into hair are not known. In this study, we examined the incorporation of a weak acid, phenobarbital, and a weak base, codeine, into Sprague-Dawley (SD) rat hair. Codeine or phenobarbital was administered to male SD rats at 40 mg/kg/day for 5 days by intraperitoneal (ip) injection. Hair was collected from the back 14 days after beginning the 5-day dosing protocol and analyzed by gas chromatography/mass spectrometry (GC/MS) for codeine and phenobarbital. The time-courses of phenobarbital and codeine in plasma were also obtained after a single ip injection (40 mg/kg). Concentrations of codeine and phenobarbital in SD hair samples were 0.98 +/- 0.10 and 17.01 +/- 1.40 ng/mg hair. respectively. The areas under the curve (AUC) of plasma concentration versus time for codeine and phenobarbital were 1.58 and 414.50 micrograms h/microL, respectively. Notwithstanding the greater phenobarbital concentrations in hair, when plasma concentrations were considered, codeine was apparently incorporated to a 15-fold greater extent than phenobarbital. Because hair pigmentation may be important in drug incorporation, the incorporation of these two drugs was also studied in Long-Evans (LE; produces both black and white hair on the same animal) rats after 40 mg/kg/day of ip drug administration for 5 days. Hair was collected at the same time as the previous experiment. Concentrations of codeine in hair were 44-times greater in pigmented than nonpigmented hair from the same animals. In contrast, hair concentrations of phenobarbital were identical in both pigmented and nonpigmented hair. These data suggest that hair pigmentation greatly affects weak base incorporation but not weak acid incorporation into hair. Because hair concentrations of phenobarbital are not affected by pigmentation, phenobarbital may be an ideal drug to separate out factors other than pigmentation involved in incorporation of drugs into hair.
血液中循环的药物和内源性化合物最终可能会融入生长中的毛干。滥用药物的毛发分析是法医和临床毒理学领域中一个不断发展的领域。然而，药物融入毛发的潜在机制尚不清楚。在本研究中，我们检测了弱酸苯巴比妥和弱碱可待因融入斯普拉格-道利（SD）大鼠毛发的情况。通过腹腔注射以40mg/kg/天的剂量给雄性SD大鼠注射可待因或苯巴比妥，持续5天。在为期5天的给药方案开始14天后，从大鼠背部采集毛发，并通过气相色谱/质谱联用仪（GC/MS）分析其中的可待因和苯巴比妥。单次腹腔注射（40mg/kg）后，还获取了血浆中苯巴比妥和可待因的时间进程。SD大鼠毛发样本中可待因和苯巴比妥的浓度分别为0.98±0.10和17.01±1.40ng/mg毛发。可待因和苯巴比妥血浆浓度-时间曲线下面积（AUC）分别为1.58和414.50μg·h/μL。尽管毛发中苯巴比妥浓度更高，但考虑血浆浓度时，可待因融入毛发的程度显然比苯巴比妥高15倍。由于毛发色素沉着可能在药物融入过程中起重要作用，在以40mg/kg/天的剂量腹腔注射药物5天后，我们也在朗-埃文斯（LE；同一动物身上既有黑色毛发又有白色毛发）大鼠中研究了这两种药物的融入情况。毛发采集时间与之前的实验相同。同一动物有色毛发中的可待因浓度比无色毛发中的高44倍。相比之下，有色毛发和无色毛发中苯巴比妥的毛发浓度相同。这些数据表明，毛发色素沉着对弱碱融入毛发有很大影响，但对弱酸融入毛发没有影响。由于苯巴比妥的毛发浓度不受色素沉着影响，苯巴比妥可能是一种理想的药物，可用于分离出除色素沉着外其他参与药物融入毛发的因素。
