Examination of postmortem fluids and tissues for the presence of methylecgonidine, ecgonidine, cocaine, and benzoylecgonine using solid-phase extraction and gas chromatography-mass spectrometry.
On the basis of this information, it would be reasonable to expect individuals smoking crack COC to inhale significant amounts of MED. As a result, the detection of MED would be a valuable marker to aid in identifying smoking as a route of administration and in estimating COC concentrations at the time of death.
There are additional considerations in the analysis of MED. Once in the body, the concentration of MED might be expected to be lower because of conversion to ecgonidine (ED). The hydrolysis of MED to ED has been reported, and ED has been detected in human urine (7, 8). Urine specimens that had tested positive for benzoylecgonine (BZ) in the military drug-testing program were tested for MED and ED. In 22 of the 23 specimens tested, ED was detected, and the concentrations were at least an order of magnitude greater than those of MED. These results suggest the value of quantifying both MED and ED to identify COC smoking as the route of administration.
Although MED and/or ED have been examined in various tissues and fluids (2, 3, 7-13), MED has not been examined in liver and brain tissue, and ED has not been examined in liver, brain, and blood specimens. We examined the available specimens from 15 postmortem cases for the presence of MED, ED, COC, and BZ.
Materials and Methods
CHEMICALS, REAGENTS, AND SUPPLIES
N-desmethyl-N-[[sup.2.H.sub.3]]methylcocaine ([d.sub.3] COC), BZ, N-des-methyl-N-[[sup.2.H.sub.3]]methylbenzoylecgonine ([d.sub.3]-BZ), N-desmethyl-N-[[sup.2.H.sub.3]]methylecgonine ([d.sub.3]-EC), ecgonine, MED (anhydroecgonine methyl ester), and ED (anhydroecgonine) were purchased from Radian International. COC (free base) was purchased from Sigma Chemical, and dimethylformamide (DMF), DMF dipropyl acetal (DMF-DPA), and DMF dimethyl acetal were purchased form Aldrich Chemical. Solid-phase extraction (SPE) columns containing silica-based [C.sub.8] and S[O.sub.3]H (200 mg) and a glass extraction chamber were purchased from United Chemical Technologies. Reacti-vials, bis(trimethylsilyl)trifluoroacetamide (BSTFA), and N-methyl-N-(tert-butyldimethylsilyl)trifluoroacetamide (MTBSTFA) containing 1% tert-butyldimethylchlorosilane (TBDMCS) were purchased from Pierce. All solvents and reagents were analytical or HPLC grade. Acetone was dried over molecular sieves (3A, 8-12 mesh) for at least 24 h.
Specimens from 15 postmortem cases were obtained from the Postmortem/ Human Performance Laboratory, Division of Forensic Toxicology, Armed Forces Medical Examiners' Office, Armed Forces Institute of Pathology. The research protocol was approved by the Armed Forces Institute of Pathology Institutional Review Board. Specimens reported to be positive for COC/BZ had been screened positive by immunoassay, confirmed positive by gas chromatography-mass spectrometry (GC-MS), and stored frozen at -18[degrees]C for 6 months after testing was completed. Before use in this study, specimen identity was removed in preparation for disposal. Complete information concerning the specific source for each fluid and tissue was not available for any case. A significant impact on results was unlikely for the liver specimens because drug distribution in liver tissue would be expected to be uniform as a result of normal high hepatic profusion and metabolic activity. Brain tissue may have been obtained from various portions of the brain because there is no standardized procedure concerning the source of brain tissue. This most likely did not have a significant impact on our results, based on the reported uniform distribution of COC in postmortem brain tissue (14). Urine was obtained directly from the bladder. In a few cases, blood specimens were obtained directly from the heart or from an intravenous catheter.
The Hewlett-Packard GC-MS system consisted of an HP 5890 Series II Plus gas chromatograph and a Model 5972 quadrupole mass-selective detector. An HP 18593B auto-injector was used to inject the samples into the GC-MS instrument.
SYNTHESIS OF METHYL N-DESMETHYL-N-[[sup.2.H.sub.3]]METHYLECGONIDINE ([d.sub.3]-MED)
The starting compound, N-desmethyl-N-[[sup.2.H.sub.3]]methylecgonidine ([d.sub.3]-ED) was prepared from 200 [micro]g of [d.sub.3] EC by the procedure published previously (7). DMF dimethyl acetal (50 [micro]L) was added to the compound in a Reactivial. The vial was tightly capped, vortex-mixed, and heated at 50[degrees]C for 5 h. The solution was cooled to room temperature. The [d.sub.3]-MED, without further purification, was quantitatively transferred to a 50-mL volumetric flask and diluted to the mark with acetonitrile. When compared against a known amount of nondeuterated MED, the concentration of [d.sub.3]-MED was found to be 2.08 mg/L. On the basis of the molar concentration compared to the starting material, [d.sub.3]-ED, the yield was 84%.
PREPARATION OF STOCK SOLUTIONS
Solutions of COC, [d.sub.3] COC, MED, and [d.sub.3]-MED at appropriate concentrations were prepared in acetonitrile. Hydroxy solvents were not used to avoid hydrolysis of methyl esters. Solutions of BZ, [d.sub.3]-BZ, ED, and [d.sub.3]-ED were prepared in methanol.
SAMPLE PREPARATION FOR COC, BZ, MED, AND ED DETERMINATION
Liver and brain tissue samples. The flowchart for the extraction is shown in Fig. 1. For each specimen and control, 1 g of tissue (negative tissue for control) was weighed into flat-bottomed plastic tubes and stored frozen. Controls were prepared at concentrations of 100, 50, and 20 ng/g of tissue by adding COC (100 [micro]L of 1.0, 0.5, or 0.2 mg/L), BZ (100 [micro]L of 1.0, 0.5, or 0.2 mg/L), MED (100 [micro]L of 1.0, 0.5, or 0.2 mg/L), and ED (100 [micro]L of 1.0, 0.5, or 0.2 mg/L) into three empty glass centrifuge tubes. Internal standards (100 [micro]L of 0.5 mg/L [d.sub.3] COC, 100 [micro]L of 0.5 mg/L [d.sub.3]-BZ, 50 [micro]L of 0.68 mg/L [d.sub.3]-MED, and 100 [micro]L of 0.5 mg/L [d.sub.3]-ED) were added to the control tubes and to empty glass centrifuge tubes that were later used for specimen analysis.
[FIGURE 1 OMITTED]
Freshly prepared NaF (200 [micro]L; 10 g/L) was added to the tissues in the plastic tubes. The tissues were thawed, homogenized with 1 mL of 0.1 mol/L phosphate buffer (pH 6.0), and poured into the corresponding glass tubes containing drugs and internal standards for controls and internal standards only for specimens. Two milliliters of 0.1 mol/L phosphate buffer (pH 6.0) was then added to the residual tissue and homogenized again. The resulting homogenate was combined with the initial homogenate.
After homogenization, the tubes were capped and placed in an ice bath. The homogenates were vortex-mixed for 10-15 s and centrifuged for 60 min at 3834g at 7-10[degrees]C. A set of SPE columns was placed in the extraction chamber and conditioned with 3 mL each of methanol, water, and 0.1 mol/L phosphate buffer (pH 6.0), in that sequence, under slightly reduced pressure.
A set of glass centrifuge tubes was placed in the chamber to collect the next elution fraction (containing ED). The supernatants from the tissue homogenates were poured onto the columns and allowed to elute by gravity or under slightly reduced pressure. Deionized water (1 mL) was added to the columns, and that fraction was also collected. The tubes from the chamber were then removed and set aside for extraction of ED (Fig. 1). The SPE columns were washed with 2 mL of deionized water, 3 mL of 0.1 mol/L HCl, and 3 mL of isopropanol, and then dried for 5 min under reduced pressure. The MED, COC, and BZ were then eluted with 3 mL of a mixture (9:1:0.2 by volume) of dichloromethane-methanol-aqueous N[H.sub.3] (14.8 mol/L).
The solutions were evaporated to dryness under nitrogen at room temperature to minimize loss of MED. The extracts were dissolved in 50 [micro]L of dry acetone, transferred into autosampler vials, and tested for MED and COC by two separate GC-MS procedures. After the MED and COC tests, the samples were tested for BZ as the propyl derivative, using another GC-MS procedure.
To extract ED from the eluates, the pH of the solutions was adjusted to 2.0 [+ or -] 0.2 with 0.5 mol/L HCl. Methylene chloride (1 mL) was added to each tube and vortex-mixed. The solutions were centrifuged at 2177g for 3 min. The clear upper aqueous layers were then poured onto a second set of SPE columns preconditioned with 3 mL of methanol, 3 mL of deionized water, and 1 mL of 0.01 mol/L HCl. The solutions were allowed to elute by gravity flow or under slightly reduced pressure. The columns were washed with 1 mL of 0.1 mol/L HCl and 3 mL of methanol, and dried under reduced pressure for 5 min. The ED was eluted with 3 mL of a mixture (4:6:0.25 by volume) of methanol-isopropanol-aqueous N[H.sub.3] (14.8 mol/L). The solutions were evaporated under nitrogen at 50[degrees]C. To remove the white residue from ED, 2 mL of dry acetone was added. The solutions were vortex-mixed and centrifuged. The acetone solutions were separated and evaporated to dryness. The liver specimens were tested for ED as the tert-butyldimethylsilyl derivative by a GC-MS method, and the brain specimens were tested for ED as the trimethylsilyl derivative by GC-MS.
Urine and blood samples. An initial 3-mL aliquot of each urine specimen was prepared as published previously (7). The procedure used for preparing blood specimens was the same as for the liver and brain tissues with the following exceptions. The initial 1-mL aliquots of blood were diluted with 4 mL of 0.1 mol/L phosphate buffer (pH 6.0). No methylene chloride wash was used in preparing the ED-containing fractions for the SPE steps.
Propylation of BZ at the GC injection port for specimen analysis. After COC and MED analysis in acetone solution, DMF-DPA (20 [micro]L) was added to the autosampler vials. The contents were mixed, and the vials were recapped. Analysis was performed for propyl-BZ as reported previously (7).
Silylation of ED by MTBSTFA for specimen analysis. The extracts from liver and urine containing ED were dissolved in MTBSTFA containing 1% TBDMCS and prepared as described previously (7).
Silylation of ED by BSTFA for specimen analysis. The extracts from brain and blood containing ED were dissolved in 50 [micro]L of BSTFA and heated in closed tubes at 70[degrees]C for 15 min. The samples were centrifuged immediately at 7-10[degrees]C for 2-3 min at 1700g and transferred to autosampler vials for GC-MS analysis.
Samples were introduced in 1- to 4-[micro]L volumes using an autoinjector. The GC analysis was performed using a DB-5MS capillary column [5:95 phenyl-methylsiloxane; 15 m x 0.25 mm (i.d.); J & W Scientific] or a ZB-5 [5% phenyl polysiloxane; 15 m x 0.25 mm (i.d.); Phenomenex] at 10 psi constant pressure helium flow. The mass-selective detector was operated in the electron ionization mode at 70 eV with a source temperature of 200-250[degrees]C. The electron multiplier voltage of the detector was set at 200-700 V above autotune, and the dwell time for each ion monitored was 50 ms.
GC-MS conditions for MED. The analysis was performed at injector and transfer line temperatures of 140 and 280[degrees]C, respectively. The oven temperature started at 90[degrees]C (held for 1 min) and increased to 140[degrees]C at 20[degrees]C/min (held for 2 min). The GC was started in splitless mode, and injector port purge was turned on after 0.3 min. The monitored ions were m/z 181, 166, and 152 for MED and m/z 184 and 155 for the [d.sub.33]-MED. Ions m/z 152 and 155 were used for quantification. Because COC, BZ, and MED were extracted together, injector temperatures were kept [less than or equal to] 140[degrees]C to avoid possible formation of MED from any COC present in the sample. After each injection, 2-3 [micro]L of acetone was injected as a solvent blank.
GC-MS conditions for COC. The analysis was performed at injector and transfer line temperatures of 280 and 270[degrees]C, respectively. The oven temperature started at 170[degrees]C (held for 0.5 min) and increased to 270[degrees]C at 30[degrees]C/min (held for 2.7 min). The GC was started in splitless mode, and injector port purge was turned on after 0.3 min. The monitored ions were m/z 303, 272, and 182 for COC and m/z 306 and 185 for the [d.sub.3] COC. Ions m/z 303 and 306 were used for quantification. After each injection, 3 [micro]L of acetone was injected as a solvent blank.
GC-MS conditions for propyl BZ. The analysis was performed at injector and transfer line temperatures of 280 and 270[degrees]C, respectively. The oven temperature started at 170[degrees]C (held for 0.5 min) and increased to 270[degrees]C at 30[degrees]C/min (held for 2.7 min). The GC was started in splitless mode, and injector port purge was turned on after 0.3 min. The monitored ions were m/z 331, 272, and 210 for BZ and m/z 334 and 213 for [d.sub.3]-BZ. Ions m/z 331 and 334 were used for quantification. After each injection, 3 [micro]L of MTBSTFA containing 1% TBDMCS was injected as a solvent blank.
GC-MS conditions for tert-butyldimethylsilyl ED. The analysis was performed at injector and transfer line temperatures of 250 and 270[degrees]C, respectively. The oven temperature started at 135[degrees]C (held for 0.5 min), increased to 175[degrees]C at 10[degrees]C/min (held for 0.5 min), and increased to 275[degrees]C at 30[degrees]C/min (held for 1 min). The GC was started in splitless mode, and injector port purge was turned on after 0.2 min. The monitored ions were m/z 281, 252, and 224 for ED and m/z 284 and 227 for the [d.sub.3]-ED. Ions m/z 224 and 227 were used for quantification. After each injection, 3 [micro]L of MTBSTFA containing 1% TBDMCS was injected as a solvent blank.
GC-MS conditions for trimethylsilyl ED. The analysis was performed at injector and transfer line temperatures of 200 and 220[degrees]C, respectively. The oven temperature started at 111[degrees]C (held for 1 min) and increased to 210[degrees]C at 25[degrees]C/min (held for 2 min). The GC was started in splitless mode, and injector port purge was turned on after 0.2 min. The monitored ions were m/z 239, 224, and 210 for ED and m/z 242 and 213 for the [d.sub.3]-ED. Ions m/z 210 and 213 were used for quantification. After each injection, 3 [micro]L of BSTFA was injected as a solvent blank.
The statistical analysis of the data sets was performed using ANOVA. To be a significant difference, both sets had to show a difference at P <0.05.
Results and Discussion
MED is a pyrolytic product of COC. Both MED and ED are also produced as artifacts from COC or COC metabolites during GC-MS analysis (7). Therefore, suitable analytical conditions are necessary to test MED and ED in body fluids and tissues. In the extraction, ED was separated from other drugs by selective adsorption on the SPE columns ([C.sub.8] and S[O.sub.3]H). At pH 6.0 [+ or -] 0.5, most of the COC, BZ, and MED (>90%) were retained on the column, whereas ED, which did not adsorb, passed through the column and was collected. ED was then extracted from the solution by adjusting the pH to 2-3 and allowing it to pass through a second column. At this pH, ED was more lipophilic and suitable for column adsorption. The compound was then eluted with a mixture of polar solvents [methanol-isopropanol-ammonia (4:6:0.25 by volume)]. To elute MED, COC, and BZ from the first column, dichloromethane-methanol-ammonia (9:1:0.2 by volume) was preferred over the generally used dichlorobutane-isopropanol-ammonia (8:2:0.2 by volume) because MED is volatile and easily lost during evaporation of the higher boiling isopropanol.
[FIGURE 2 OMITTED]
Separation of ED from COC and COC metabolites minimized the formation of artifact ED. MED in the extract of COC and BZ was analyzed separately at a GC injection port temperature of [less than or equal to] 140[degrees]C. Higher temperatures were avoided to minimize formation of artifact MED. To ensure that artifacts were not formed during analysis, a control containing COC, BZ, EC, and MEC at 1, 5, 5, and 5 mg/L, respectively, was tested. No ED or MED was detected under the extraction and GC-MS conditions described. COC was also injected separately before derivatization of BZ because the alkylating agents contained a small amount of methylating agent as impurity. In our experiment, DMF-DPA, DMF-diisopropylamide, or DMF-diethylamide with only BZ produced a small amount of COC as byproduct (<1%). Although MED and COC were injected under two different conditions (injection temperatures 140 and 280[degrees]C, respectively), the samples could be analyzed in one injection batch by use of an autoinjector with two GC-MS settings. ED extracted from blood and brain and tested as the tert-butyldimethylsilyl derivative showed chromatographic background. Analyzing the compound as the trimethylsilyl derivative minimized the background.
The linearity, correlation coefficient squared ([r.sup.2]), limit of quantification (LOQ), and extraction efficiency are summarized in Table 1. In the range of linearity, all compounds showed ion ratios within [+ or -] 20% of the mean values. At least eight concentrations were used in the range of linearity. Only one sample was tested at each concentration. Good correlation [r.sup.2] was observed in the linear range mentioned, where acceptable values were defined as [greater than or equal to] 0.9900. Signal-to-noise ratios in all analyses were >4:1. In this study, LOQ was defined as the concentration at which one of the two ion ratios was outside [+ or -] 20% but within [+ or -] 30% and the concentration was within [+ or -] 20% of expected value. Quantification ions in some compounds showed better chromatographic background, allowing a LOQ below the limit of linearity. This observation was most likely attributable to the variability of the biological matrices among the various tissues and fluids. Specimens were analyzed in several batches, and controls at concentrations of 0, 20, 50, and 100 [micro]L were used in each batch analysis to validate the results. The criteria for batch validation were the same as those used for linearity studies.
Case histories for the specimens were extremely limited, although preliminary causes of death were not attributed to drug overdose. The results from the analyses by drug are summarized in Tables 2 and 3. Fig. 2 shows chromatograms for ED extracted from blood specimen 4 (Fig. 2a) and MED extracted from brain specimen 11 (Fig. 2b), where the concentrations were 25 [micro]g/L and 22 ng/g, respectively. The ranges for MED concentrations in liver, brain, blood, and urine were 0-10 ng/g, 0-92 ng/g, 0-42 [micro]g/L, and 0-2030 [micro]g/L, respectively. The number of samples in which MED was detected was 5 of 15, 7 of 14, 3 of 11, and 10 of 13 in liver, brain, blood, and urine, respectively. Although MED was detected in 5 of 15 liver specimens, the observed concentrations did not exceed 10 ng/g in any specimen. In contrast, urine concentrations as high as 2030 [micro]g/L were observed, and 6 of the 13 urine specimens reached concentrations in excess of 100 [micro]g/L. In general, MED concentrations were much lower in brain than in urine. The range of MED concentrations in the liver specimens was slightly larger than in the brain specimens. Although examining brain for estimating COC concentrations at the time of death may have some advantage because of the free passage of COC across the blood-brain barrier, the characteristics of MED relative to the blood-brain barrier have not been established. The high number of blood samples negative for MED or with low MED concentrations may indicate that detection of MED may be difficult in blood and be of limited usefulness in the estimation of COC concentrations at the time of death. On the basis of these observations along with other concerns for the use of blood in evaluating COC use in postmortem cases (15), other tissues and/or fluids may be more useful in postmortem examinations.
ED concentrations were noticeably higher than MED in liver, blood, and urine. In liver, the median ED concentration was 655 ng/g (range, 90-3274 ng/g) compared with 0 ng/g (range, 0-10 ng/g) for MED. Similar results were observed in blood. The amount of ED was relatively low in brain, and there was no statistical difference compared with MED concentrations in brain tissue. This indicates that ED does not easily pass through the blood-brain barrier, which might be expected based on the hydrophilic nature of ED, and may also be accompanied by extensive first- or second-pass metabolism of MED in the liver and efficient excretion of ED by the body via the kidneys. This may also indicate that any MED that may enter the brain is converted to ED via enzymatic hydrolysis at a very low rate, which may parallel the observation that cocaine methyl esterase activity in brain is only 1-6% compared with liver in rats (16). Although MED was detected in only 3 of 11 blood specimens, ED was detected in all blood specimens. This suggests that MED is extensively converted to ED in the blood as well as in the liver, which is supported by the previously reported hydrolysis of MED to ED in liver homogenates (7) and the enzymatic hydrolysis observed in unpreserved sheep plasma (17).
When the ED concentrations in liver and urine were compared, 6 of 13 specimens contained more ED in liver than in urine. In 8 of 15 liver specimens, the amount of ED actually exceeded the amount of BZ. ED was detected in all 15 cases (50 of 53 total specimens), indicating that smoking was a route of COC administration. Compared with the detection of MED in 12 of 15 cases (25 of 53 total specimens), ED appears to be more easily detected than MED and may be a more useful marker than MED for determination of COC smoking in postmortem cases.
In conclusion, a review of the data reveals that ED concentrations were significantly higher than MED concentrations in liver, blood, and urine. In brain the difference was not significant. Of 53 tissue and fluid specimens collected from 15 postmortem cases, 50 specimens were positive for ED compared with only 25 specimens positive for MED. Only three brain specimens were negative for ED. The presence of ED and MED suggests that smoking was the route of COC administration in all 15 postmortem cases.
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ERIC T. SHIMOMURA, GWENDOLYN D. HODGE, and BUDDHA D. PAUL *
Division of Forensic Toxicology, Office of the Armed Forces Medical Examiner, Armed Forces Institute of Pathology, Rockville, MD 20850.
The opinions expressed herein are those of the authors and are not to be construed as official or as reflecting the views of the Department of the Army, the Department of the Navy, the Department of the Air Force, or the Department of Defense.
 Nonstandard abbreviations: COC, cocaine; MED, methylecgonidine; ED, ecgonidine; BZ, benzoylecgonine; [d.sub.3]-COC, N-desmethyl-N-[[sup.2.H.sub.3]]methylcocaine; [d.sub.3]-BZ, N-desmethyl-N-[[sup.2.H.sub.3]]methylbenzoylecgonine; [d.sub.3]-EC, N-desmethyl-N-[[[sup.2.H.sub.3]]]methylecgonine; DMF, dimethylformamide; DMF-DPA, DMF dipropyl acetal; SPE, solid-phase extraction; BSTFA, bis(trimethylsilyl)trifluoroacetamide; MTBSTFA, N-methyl-N-(tert-butyldimethylsilyl)trifluoroacetamide; TBDMCS, tert-butyldimethylchlorosilane; GC-MS, gas chromatography mass spectrometry; [d.sub.3]-MED, methyl N-desmethyl-N-[[sup.2.H.sub.3]]methylecgonidine; [d.sub.3]-ED, N-desmethyl-N-[[sup.2.H.sub.3]]methylecgonidine; and LOQ, limit of quantification.
* Address correspondence to this author at: Division of Forensic Toxicology, AFIP Annex, 1413 Research Blvd., Rockville, MD 20850. Fax 301-319-0628; e-mail email@example.com.
Received January 10, 2001; accepted March 12, 2001.
Table 1. Linearity, correlation coefficient squared ([r.sup.2]), LOQ, and extraction efficiency for MED, ED, COC, and BZ from postmortem specimens. Linearity, LOQ, (a) Extraction [mu] g/L [r.sup.2] [mu] g/L efficiency, % Liver MED 6-150 0.9982 5 >90 ED 20-500 0.9989 10 50-60 COC 20-500 0.9966 5 >90 BZ 20-500 0.9991 5 >90 Brain MED 20-300 0.9994 5 >90 ED 20-500 0.9971 10 50-60 COC 15-2000 0.9992 5 >90 BZ 15-2000 0.9969 5 >90 Blood MED 20-300 0.9982 5 >90 ED 20-300 0.9989 10 50-60 COC 10-500 0.9966 5 >90 BZ 10-500 0.9991 5 >90 Urine MED 2-300 0.9965 2 >90 ED 10-300 0.9979 10 50-60 COC 5-500 0.9933 5 >90 BZ 5-500 0.9996 5 >90 (a) When LOQ was below the lowest limit of linearity, one of the ion ratios was outside [+ or ] 20%, but quantification was within [+ or -] 20% of the expected value. Table 2. Drug concentrations in liver and brain from 15 postmortem specimens. (a) Liver, ng/g Specimen MED ED COC BZ 1 0 90 0 60 2 0 132 0 68 3 0 221 66 612 4 0 293 0 45 5 0 334 21 149 6 0 428 11 440 7 0 596 57 103 8 0 655 9 821 9 0 1131 21 890 10 0 2582 426 1643 11 5 1406 134 2755 12 6 1644 103 3513 13 8 1950 503 4980 14 8 2134 77 2963 15 10 3274 270 2430 Median 0 655 57 821 Range 0-10 90-3274 0-503 45-4980 Positive 5/15 15/15 12/15 15/15 Brain, ng/g Specimen MED ED COC BZ 1 0 7 0 3078 2 0 0 0 46 3 92 0 1403 474 4 0 0 0 47 5 0 48 33 61 6 0 12 37 283 7 NA (b) NA NA NA 8 0 22 8 1489 9 0 22 14 290 10 31 52 336 222 11 22 26 863 592 12 17 43 704 5153 13 14 40 546 2707 14 29 17 707 2982 15 19 34 490 574 Median 7 22 187 524 Range 0-92 0-52 0-1403 46-5153 Positive 7/14 11/14 11/14 14/14 (a) Values of 0 indicate quantification below the LOQ. (b) NA, specimen not available. Table 3. Drug concentrations in blood and urine from 15 postmortem specimens. (a) Blood, [mu] g/L Specimen MED ED COC BZ 1 0 13 0 30 2 0 36 0 60 3 NA (b) NA NA NA 4 0 25 0 32 5 NA NA NA NA 6 0 60 5 332 7 0 299 30 87 8 0 29 5 458 9 0 119 13 628 10 11 214 35 1543 11 0 314 20 1519 12 NA NA NA NA 13 42 143 12 2071 14 8 773 88 1831 15 NA NA NA NA Median 0 119 12 458 Range 0-42 13-773 0-88 30-2071 Positive 3/11 11/11 8/11 11/11 Urine, [mu] g/L Specimen MED ED COC BZ 1 0 126 37 917 2 0 468 155 2084 3 62 109 1918 1736 4 0 146 63 999 5 48 456 1229 6768 6 14 226 185 3948 7 132 307 1119 1705 8 40 296 475 14 748 9 116 1143 1208 19 740 10 NA NA NA NA 11 1299 1826 13 520 42 462 12 2030 7452 20 528 116 430 13 616 1116 28 062 39 624 14 999 2729 4214 107 868 15 NA NA NA NA Median 62 456 1208 6768 Range 0-2030 109-7452 37-28 062 917-116 430 Positive 10/13 13/13 13/13 13/13 (a) Values of 0 indicate quantification below the LOQ. (b) NA, specimen not available.
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|Title Annotation:||Drug Monitoring and Toxicology|
|Author:||Shimomura, Eric T.; Hodge, Gwendolyn D.; Paul, Buddha D.|
|Date:||Jun 1, 2001|
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