Can a Child Be Taking From a Mother and Daddy of a Baby Test Positive for Meth

Ther Drug Monit. Author manuscript; available in PMC 2014 Dec 1.

Published in final edited grade as:

PMCID: PMC3838616

NIHMSID: NIHMS479006

Identifying methamphetamine exposure in children

Marisol Southward. Castaneto, M.Due south.,¹ Allan J. Barnes, B.Sc.,^one Karl B. Scheidweiler, Ph.D.,¹ Michael Schaffer, Ph.D.,ⁱⁱ Kristen K. Rogers, Chiliad.D.,³ Deborah Stewart, M.D.,^four and Marilyn A. Huestis, Ph.D.¹

Marisol S. Castaneto

¹Chemical science and Drug Metabolism, NIDA-IRP, NIH, Baltimore, Doctor, Us

Allan J. Barnes

ⁱChemistry and Drug Metabolism, NIDA-IRP, NIH, Baltimore, Physician, United states of america

Karl B. Scheidweiler

ⁱChemistry and Drug Metabolism, NIDA-IRP, NIH, Baltimore, Md, USA

Michael Schaffer

²Psychemedics Corporation, Culver City, CA

Kristen M. Rogers

³California Department of Public Health, Sacramento, CA

Deborah Stewart

⁴California State Academy, Chico, CA

Marilyn A. Huestis

^oneChemistry and Drug Metabolism, NIDA-IRP, NIH, Baltimore, Doctor, The states

Abstract

Introduction

Methamphetamine (MAMP) use, distribution and industry remain a serious public health and safety problem in the Us, and children environmentally exposed to MAMP face a myriad of developmental, social and health risks, including severe abuse and neglect necessitating child protection involvement. It is recommended that drug-endangered children receive medical evaluation and care with documentation of overall physical and mental conditions and take urine drug testing.¹ The primary aim of this study was to decide the best biological matrix to detect MAMP, amphetamine (AMP), methylenedioxymethamphetamine (MDMA), methylenedioxyamphetamine (MDA) and methylenedioxyethylamphetamine (MDEA) in environmentally exposed children.

Method

91 children, environmentally exposed to household MAMP intake, were medically evaluated at the Child and Adolescent Abuse Resource and Evaluation (CAARE) Diagnostic and Handling Center at the University of California, Davis (UCD) Children's Hospital. MAMP, AMP, MDMA, MDA and MDEA were quantified in urine and oral fluid (OF) past gas chromatography mass spectrometry (GCMS) and in pilus past liquid chromatography tandem mass spectrometry (LCMSMS).

Results

Overall drug detection rates in OF, urine and hair were six.9%, 22.one% and 77.8%, respectively. Lxx children (79%) tested positive for i or more than drugs in 1 or more matrices. MAMP was the chief analyte detected in all iii biological matrices. All positive OF (north=v) and eighteen of nineteen positive urine specimens also had a positive hair test.

Determination

Hair analysis offered a more than sensitive tool for identifying MAMP, AMP and MDMA environmental exposure in children than urine or OF testing. A negative urine, or hair test does not exclude the possibility of drug exposure, just hair testing provided the greatest sensitivity for identifying drug-exposed children.

Keywords: hair, urine, oral fluid, drug-exposed children, methamphetamine

Introduction

Methamphetamine (MAMP), a sympathomimetic amine, is a powerful central nervous system stimulant with limited medical indications including attending deficit hyperactivity disorder and obesity.² MAMP is an addictive substance that produces euphoria and a sense of well-existence, suppresses appetite, and increases alertness and energy.^three It is 1 of the 5 almost unremarkably abused illicit drugs in Due north America, Europe and Southeast Asia.⁴ Adverse effects of MAMP intake range from mild to life-threatening symptoms such as agitation, tremor, dyspnea, tachycardia, nausea, vomiting, psychosis, hypertension, stroke, and coma.^{2-3, five}

Illicit MAMP is typically produced in clandestine laboratories that are often small-scale and poorly-ventilated.⁶ Prior to March 2006, illicit MAMP production involved cheap and like shooting fish in a barrel-to-obtain chemicals, including the precursor pseudoephedrine, which was bachelor over-the-counter. The Combat Methamphetamine Epidemic Act of 2005 amended the Controlled Substance Abuse human action requires retail stores (and their employed pharmacists) to receive grooming and obtain certification prior to dispensing non-prescription drugs containing ephedrine, pseudoephedrine and phenylpropanolamine.^vii Although this provision decreased the corporeality of pseudoephedrine bachelor for illicit MAMP production in the US, a new method and so-chosen "shake and bake" or "one-pot" method was developed in contempo years.⁸ This method allowed chemists to manufacture the drug using a small amount of pseudoephedrine and synthesize MAMP in ten min or less. In improver, MAMP producers found a mode to bypass regulations on express pseudoephedrine procurement past working in groups ("smurfing"), using false identifications, and traveling from one pharmacy to another.^8-nine At that place were vi,768 MAMP laboratory seizures in 2010, a 12% increment from the previous year (6,032).⁸ The National Drug Intelligence Heart predicted that small-scale laboratories will remain a substantial source of MAMP, along with "super meth labs" controlled by large drug-trafficking organizations, to provide cheap, high-purity MAMP.⁸

Chemicals such as anhydrous ammonia, sodium hydroxide, sulfuric acid, alcohols, and other solvents utilized in illicit MAMP production are toxic, chancy, and volatile. Thus, the surround of a clandestine MAMP laboratory is inherently hazardous to inhabitants, including children living with the adult operators.^10-13 Children taken from these home-based MAMP laboratories are exposed to toxic fumes, accidental burns, and contaminated drug paraphernalia. Chronic adult MAMP apply is associated with psychosis, severely dumb judgment, agitation, hypersexuality, preoccupation with guns and violence, and frequent association with a criminal lifestyle. Thus, children of chronic MAMP users are poorly fed, improperly clothed, inadequately schooled, and lack good hygiene, as their parents (or caregivers) go through crash and binge cycles, and nigh often sleep through meal and school times.^{half dozen, 12-thirteen} Children taken into custody from drug-exposed environments by Child Protection Services (CPS) are classified as drug-endangered children (December),regardless of the source of exposure.¹ The US Department of Justice recently established a program ("Drug Endangered Children Task Forcefulness") in response to the overwhelming need to protect children from exposure to drug environments.^ane

At that place are no standard guidelines for state and local agencies to deed on Dec cases.^{6, eleven, thirteen-17} When a child is taken into CPS custody, drug exposure is more often than not evaluated with urine testing.^{13-fourteen, 16-xviii} Collection of urine is non-invasive, normally of adequate volume, and testing is readily available and reliable, but urine offers only a ii-iii day window of drug detection, and available cutoff concentrations are high and poorly sensitive to identify depression-level MAMP ecology exposure.^19-21

An alternative biological matrix is oral fluid (OF) that is now widely accustomed in clinical, workplace and driving nether the influence of drugs settings.^twenty Like to urine, drug detection times in OF are short, upward to about 48 h afterwards terminal exposure.²² In dissimilarity, drug testing in hair offers a wider window of detection than urine and OF, depending upon hair length.^23-24 Some state laws mandate that a kid under CPS custody with a positive urine drug test be removed from the source of exposure until appropriate measures can be taken.^{half dozen, thirteen} If the drug test is negative, by and large the child is returned to the home, and discipline to further toxic exposures.

The goal of this study was to determine the all-time biological matrix for identifying children exposed to MAMP, amphetamine (AMP), three,4-methylenedioxymethamphet-amine (MDMA), 3,4-methylenedioxyamphetamine (MDA), and/or iii,4-methylenedioxy-ethylamphetamine (MDEA) past comparing detection rates in concurrently collected urine, hair, and OF specimens from drug-exposed children.

Materials and Methods

Report Participants

The study was conducted at the Child and Adolescent Abuse Resource and Evaluation (CAARE) Diagnostic and Treatment Center at the University of California, Davis (UCD) Children'south Infirmary, Sacramento, CA. The Institutional Review Board of UCD and the Sacramento County Department of Health and Human Services (DHHS) canonical this study. Within two -iii h after placement under CPS custody, drug-exposed children (ane month to 18 years onetime) were referred to the CAARE centre for medical and forensic examinations. Specimens were de-identified after drove to protect confidentiality and ensure that results could non be traced back to a CPS custody case.

Biological Specimens

Urine specimens were nerveless as office of CAARE'due south standard operating procedures for DEC referred cases. An aliquot of urine was used for routine toxicological screening, while the remaining sample was utilized for this study. OF samples were collected via the Intercept® collection device (OraSure Technologies, Inc., Bethlehem, PA, USA).

Proximal 3.ix cm pilus segments (approximately 10 mg), cutting from the crown and equally close to the root as possible, were collected from each kid.

Urine and OF were analyzed at the Chemistry and Drug Metabolism laboratory, Intramural Research Program, National Institute on Drug Abuse (NIDA), in Baltimore, Md. Hair samples were analyzed at the Psychemedics Corporation (Culver City, CA, Us).

Reagents

AMP, AMP-d_xi, MAMP, MAMP-d₁₄, MDA, MDA-d₅, MDMA, MDMA-d_five, MDEA, MDEA-d_six were purchased as racemic mixtures from Cerilliant Corporation (Circular Stone, TX, USA). Heptafluorobutyric acid anhydride (HFAA) was acquired from Pierce Chemical Co. (Rockford, IL, USA). HPLC form solvents and American Chemic Society grade ammonium hydroxide, acerb acid, concentrated hydrochloric acid, potassium phosphate monobasic, and potassium phosphate dibasic were obtained from JT Baker (Phillipsburg, NJ, Usa). SPEC C18AR/MP1 solid stage extraction (SPE) columns were from Agilent Technologies (Santa Clara, CA, USA).

Specimen Preparation and Analysis

Urine specimens, calibrators, and controls were analyzed with minor modifications to a previously published method.²⁵ Briefly, urine specimens (1 mL) fortified with internal standards were hydrolyzed with 100 μL of concentrated muriatic acid at 120 °C for xl min. After hydrolysis, 100 μL 10 N sodium hydroxide and 3 mL 0.1 M phosphate buffer (pH six.0) were added. Specimens were loaded onto preconditioned SPE columns and eluted with methylene chloride/2-isopranol/ammonium hydroxide (78:twenty:2 v/v). Eluates were reconstituted with 0.1M triethylamine in heptane (100 μL) and ten μL HFAA before derivatization for xxx min at 60°C. Derivatized extracts were cooled at room temperature prior to adding 200 μL of 0.one M phosphate buffer (pH 7.4). Samples were vortexed, centrifuged and the upper organic layer transferred to an autosampler vial and quantified past gas chromatography mass spectrometry (GCMS).

OF specimens, calibrators, and controls were analyzed by a previously published assay with minor modifications.²⁶ Briefly, 400 μL Orasure specimens, containing 133 μLOF and 267 μL elution buffer, were fortified with internal standards and diluted with 2 mL of 0.1 K potassium phosphate buffer (pH vi.0) prior to application onto preconditioned SPE columns. Columns were washed with 1 mL0.1 M acetic acrid followed by 1 mL hexane and 2 mL methanol. Columns were dried for ii min subsequently acetic acid, 1 min afterward hexane and two min after methanol washes. Analytes were eluted with 1.five mL ethyl acetate:methanol:ammonimum hydroxide (78:xx:ii, v/v/v) elution solvent. Eluates were reconstituted with 0.1 Thousand triethylamine in heptane (100 μL) and 10 uL HFAA before derivatization for twenty min at sixty°C. Derivatized samples were cooled to room temperature prior to adding 200 uL of 0.1M phosphate buffer (pH vii.iv). Samples were vortexed and the upper organic layer transferred to an autosampler vial and quantified past GCMS.

Hair specimens were treated according to the Psychemedics Corporation hair testing protocol.^27-28 Briefly, 5 – 10 mg pilus specimens were done with 100% isopropyl booze for xv min in a shaking h2o bath at 37°C, followed by three 0.1 M phosphate buffer washes (pH half dozen.0) for ane h with each wash. Pilus specimens were digested with a low pH proprietary solution containing DTT, protease Chiliad and Cholic acid solution in a shaking h2o bath for half dozen h at 37 °C.

GCMS analysis of urine and OF specimens was performed with an Agilent 6890 GC interfaced with Agilent 5973 mass selective detector operating in electron impact (EI) selected ion monitoring (SIM) mode. A DB-35ms capillary column (xv m × 0.32 mm, internal diameter × 0.25 μm picture thickness) was employed for urine testing and a HP-5ms capillary column (30 k × 0.32 mm, internal bore × 0.25 μm motion-picture show thickness) for OF analyses. GCMS parameters were based on previously published methods [26-27]. Limits of quantification (LOQ) for all analytes were 25 ng/mL (urine) and 15 ng/mL (OF). Urine calibration curves were linear from 25-5000 ng/mL for all analytes and OF calibration curves from 15 – 1500 ng/mL. Three quality control samples with concentrations beyond the linear dynamic range of the assay were analyzed in triplicate in each batch.

Three ions for each analyte and two for each deuterated internal standard were monitored for urine and OF analyses. The following ions were monitored (quantitative ions are underlined): AMP 240, 91, 118; AMP-d₁₁ 244, 98; MAMP 254, 118, 210; MAMP-d₁₄ 261, 213; MDA 162, 135; MDA-d_v 167, 380; MDMA 254,162, 210; MDMA-d₅ 258, 213; MDEA 268,162, 240; and MDEA-d₆ 274, 244.

Hair specimen extracts were analyzed based on a previously published analysis with small modifications.²⁷ Tandem liquid chromatography-mass spectrometry (LCMSMS) analysis of amphetamines in hair was performed on a Perkin Elmer Sciex API 2000.HPLC column: Betasil C₈ (2 mm × fifty mm, internal diameter × five μm particle size) with a mobile phase mixture of water and acetonitrile (86:14) with 0.1% formic acrid for MAMP and AMP analysis, while a mobile phase mixture of water and acetonitrile (81:19) with 0.i% formic acid was utilized for MDMA, MDA and MDEA. HPLC was operated in isocratic style. The mass spectrometer was operated in positive multiple reaction mode (MRM). Two independent injections were performed: the commencement was for MAMP and AMP and the 2nd for MDMA, MDEA and MDA. LOQs for MAMP/MDMA/MDEA were 0.1 ng/mg, AMP 0.025 ng/mg and MDA 0.02 ng/mg in hair. Each analysis independent quality control samples (at least 10% per batch) beyond the dynamic range of the assay.

Two ions for each analyte and deuterated internal standard were monitored for hair analysis. The ions were (quantitative ions underlined): AMP 136, 91; AMP-d₈ 144, 96; MAMP 150, 91; MAMP-d₁₁ 161, 96; MDA 180, 135; MDA-d_v 185, 137; MDMA 194, 135; MDMA-d₅ 199, 136; MDEA 208, 163; MDEA-d₆ 214, 166.

Data Analysis

Specimens with whatever analyte equal to or greater than the LOQ were considered positive. Urine and OF samples were quantified by linear regression with 1/× weighting. MSD Agilent Chemstation software was utilized to calculate peak area ratios of target analytes and internal standards for GCMS analyses. A linear curve fit forced through the origin from a single point calibration per analyte was utilized for hair samples' quantification. Statistical analyses were performed with GraphPad Prism v.v (GraphPad Software, San Diego, CA).

Results

Xc-one children enrolled in the written report and provided at to the lowest degree one specimen. Hair, urine, and OF specimens were collected from 89, 86, and 70 children, respectively. Participants' demographic characteristics and results for positive MAMP, AMP and MDMA in hair samples are summarized in Table i.

Table one

Demographics and hair confirmation results from drug-exposed children admitted to the CAARE facility. Positive methamphetamine (MAMP+), amphetamine (AMP+) and methylenedioxymethamphetamine (MDMA+) were equal or greater than limits of quantification (LOQ) of 0.1 ng/mg, 0.02 ng/mg and 0.1 ng/mg, respectively. Methylenedioxyamphetamine (MDA) and methylenedioxyethylamphetamine (MDEA) were not identified in any hair specimen.

	Total	MAMP+	AMP+	MDMA+
Demographics	Northward	N	N	N
Race/Ethnicity
Caucasian	29	24	xx	ii
African American	22	vii	two	3
Asian	vii	vii	7	0
Hispanic	18	eighteen	11	1
Mixed*	11	eight	6	iv
No information*	three	three	iii	1
Hair Colour
Blackness*	34	19	12	4
Brown	43	36	27	five
Blonde	ten	9	7	ane
No data*	3	3	3	1
Age
Under 12 months	iii	3	2	ii
1 – 18 years old**	86	64	47	9

MAMP was detected in merely five (7.1%) OF specimens; AMP (21.4 ng/mL) in only one (1.4%), which also contained the highest concentration of MAMP (133.six ng/mL). MAMP OF concentrations for specimens that tested > LOQ ranged from 17.9 to 133.6 ng/mL (median 48.6; hateful 58.2; SD 44.ix). MDMA, MDA and MDEA were < LOQ in all OF specimens.

MAMP was detected in 18 (20.nine%) urine specimens; AMP in 3 (3.5%), (ii with concurrent MAMP), for an overall detection rate of 22.1%. MAMP urine concentrations for specimens that tested > LOQ ranged from 25.1 – 107.viii ng/mL (median 0.0; hateful x.3; SD 22.4). One positive urine specimen only independent AMP only at 3851.1 ng/mL. MDMA, MDMA, and MDEA were < LOQ in all urine specimens.

MAMP, AMP, and MDMA were detected in 67 (75.3%), 49 (55.i%), and eleven (12.4%) hair specimens, respectively, for an overall detection rate of 77.8%. For specimens that tested > LOQ, MAMP hair concentrations ranged from 0.1– 22.0ng/mg (median 1.4; mean 3.3; SD 4.3), AMP concentrations were 0.025 - 1.2ng/mg (median 0.1; hateful 0.20; SD 0.25). AMP was ever present at a lower concentration than MAMP, with the exception of i hair specimen that simply contained AMP at 0.05 ng/mg. Hair AMP/MAMP ratios ranged from 0.017 to 0.115. MDMA was detected in ix of 11 pilus samples with concurrent MAMP. MDMA hair concentrations for specimens that tested >LOQ ranged from 0.10 – two.3 ng/mg (median 0.25; hateful 0.56; 0.66 SD). Among the three infants (< 12 months), MAMP was detected in all, and AMP or MDMA in two of three infants. MDA or MDEA were non detected in whatsoever pilus specimens.

70 children tested positive for at to the lowest degree one analyte in at to the lowest degree one matrix. All matrices were available from 67 children: 12 (17.9%) were drug negative in all matrices, 41 (61.2%) were positive in one matrix, 12 (17.9%) in 2 matrices and 2 (3.0%) in all iii matrices. All positive OF (northward = 5) and xviii of 19 positive urine specimens also had positive hair tests. AMP was detected alone in hair (0.05 ng/mg) and urine (3851.1 ng/mL) from the same child. Results are summarized in Table ii and Figure ane.

(A) Confirmed positive specimens for methamphetamine (MAMP), amphetamine (AMP), methylenedioxymetamphetamine (MDMA) in urine, oral fluid, and head hair concurrently nerveless specimens from 91 children. Specimens with concentrations equal to or greater than the limit of quantification (LOQ) were considered positive. Methylenedioxyamphetamine (MDA) and methylenedioxyethylamphetamine (MDEA) were not identified in whatsoever biological matrix, thus excluded from this effigy.(B) Concentrations of methamphetamine (MAMP), amphetamine (AMP), methylenedioxymethampethamine (MDMA) that quantified equal or greater than the limit of quantification (LOQ) in 89 pilus samples. MAMP concentrations (ng/mg) were plotted on the left y-axis; AMP and MDMA concentrations (ng/mg) were plotted on the correct y-axis.

Table two

Amphetamine (AMP), methamphetamine (MAMP), and methylenedioxymeth-amphetamine (MDMA) concentrations in head hair (ng/mg), urine (ng/mL) and oral fluid (ng/mL) of drug-exposed children.

	Pilus			Urine			OF
Subject	MAMP	AMP	MDMA	MAMP	AMP	MDMA	MAMP	AMP	MDMA
23	16.eight	0.8	Due north	107.8	N	N	58.1	N	N
iv	16.5	1.0	N	N	N	North	133.six	21.four	N
58	fifteen.0	0.3	0.1	94.5	26.0	N	N	N	N
40	xiv.0	0.4	N	N	N	N	N	N	Due north
13	12.3	1.2	N	42.nine	N	North	N	Due north	Due north
48	11.nine	0.i	N	32.1	N	N	North	N	Northward
74	10.2	0.iii	N	35.four	N	N	MS	MS	MS
28	nine.5	0.4	Northward	N	N	Northward	N	North	N
84	8.0	0.ii	0.2	N	N	N	MS	MS	MS
85	seven.9	0.two	0.1	35.vi	Due north	North	MS	MS	MS
59	7.6	0.3	Northward	45.8	Northward	N	N	N	N
53	6.7	0.two	N	MS	N	MS	48.6	MS	N
75	6.6	0.1	Northward	27.0	Northward	N	MS	MS	MS
90	6.5	0.3	N	MS	MS	Northward	MS	MS	MS
8	6.1	0.three	0.1	N	N	Northward	N	North	N
38	6.0	0.2	N	Due north	N	Northward	N	Northward	North
54	five.7	0.1	N	72.0	Due north	N	32.vi	Due north	N
66	4.5	0.1	0.1	17.9	Northward	Due north	Northward	N	Northward
10	3.1	0.two	N	N	N	N	Due north	N	N
fourteen	2.9	0.ii	N	31.4	Northward	N	North	N	N
29	two.viii	0.1	N	N	N	N	N	N	N
33	2.seven	0.ane	N	N	N	N	Northward	Due north	N
83	two.six	0.1	Northward	57.8	25.two	N	MS	MS	MS
63	2.6	0.1	N	N	N	N	N	N	N
37	2.v	0.2	N	61.9	N	Northward	N	N	N
36	1.8	0.1	N	41.iii	Due north	N	N	N	N
9	1.7	0.1	0.four	Northward	N	Northward	North	N	N
62	i.6	0.1	N	N	N	Due north	N	Due north	Northward
31	1.six	0.i	ii.3	MS	MS	MS	MS	MS	MS
88	1.six	N	Northward	N	N	N	MS	MS	MS
49	1.five	0.1	Northward	N	N	N	North	Northward	N
57	1.5	0.ane	N	N	N	N	MS	MS	MS
47	1.5	0.1	N	38.6	North	Northward	N	Due north	N
89	1.4	0.03	N	Northward	N	Due north	MS	MS	MS
91	i.three	0.04	North	MS	MS	MS	MS	MS	MS
34	i.3	0.one	Due north	North	North	N	Due north	N	N
55	i.3	0.03	Due north	61.v	N	N	Northward	North	Due north
threescore	one.2	N	N	North	North	N	N	N	N
50	one.2	0.04	N	N	N	N	N	N	North
15	one.0	0.1	Due north	N	N	North	Due north	N	N
39	1.0	0.04	N	N	North	North	N	N	N
64	ane.0	N	N	Northward	N	North	Northward	North	N
5	ane.0	0.04	N	N	Northward	North	N	N	North
46	0.8	0.ane	N	N	N	North	N	N	N
35	0.7	0.one	N	North	N	N	N	N	Due north
51	0.six	Northward	North	North	N	N	N	N	N
68	0.six	N	N	25.3	N	N	Due north	Northward	Northward
52	0.5	N	Northward	Northward	N	N	N	N	N
43	0.five	0.03	Due north	N	N	N	North	N	North
56	0.five	Due north	N	Northward	N	N	Northward	N	N
18	0.v	0.03	N	Due north	N	North	North	N	N
69	0.5	N	N	N	N	Due north	N	N	N
16	0.4	0.04	N	N	N	N	N	N	N
86	0.4	N	Due north	Due north	N	N	MS	MS	MS
one	0.3	0.03	N	Due north	Northward	N	Northward	Northward	N
3	0.3	N	Due north	N	N	North	N	N	N
45	0.3	N	0.3	North	Due north	Northward	N	N	N
6	0.3	N	N	N	North	N	N	Northward	N
65	0.iii	North	N	North	N	Northward	N	North	North
22	0.3	0.one	N	N	N	North	N	N	N
eleven	0.2	N	North	N	North	North	N	N	Northward
eighty	0.2	N	Due north	N	Due north	N	MS	MS	MS
44	0.2	N	N	N	N	N	N	North	N
19	0.1	N	N	Due north	N	N	N	N	N
32	0.i	Due north	0.7	N	N	N	N	N	North
27	0.1	0.03	N	33.ix	N	Due north	N	N	N
26	0.1	N	N	North	N	N	MS	MS	MS
7	N	Northward	Northward	N	Northward	N	N	N	Due north
12	Due north	N	N	N	N	Due north	Northward	N	N
17	Due north	N	North	Due north	N	North	N	Due north	N
20	Due north	Due north	N	N	N	Due north	Due north	N	Due north
21	N	N	0.eight	N	Due north	N	N	Northward	North
24	N	N	0.1	Due north	Due north	N	North	N	North
25	N	North	N	N	Due north	N	N	Northward	Due north
30	North	N	North	N	N	Northward	N	Due north	N
41	Northward	N	N	N	Northward	North	Northward	North	North
42	N	N	N	25.ane	N	Due north	N	N	N
67	North	N	North	N	Northward	N	N	N	N
70	N	N	N	N	N	N	Northward	Northward	N
71	N	Due north	N	Northward	North	N	N	Due north	N
72	N	N	N	N	Due north	North	Due north	N	N
73	N	N	Northward	North	N	N	Due north	N	N
76	Due north	N	N	North	Due north	Due north	MS	MS	MS
77	N	N	N	Northward	N	North	MS	MS	MS
78	N	North	N	N	N	N	MS	MS	MS
79	N	Northward	N	N	N	N	MS	MS	MS
81	Northward	N	Northward	N	Due north	N	MS	MS	MS
82	Northward	N	N	Northward	North	N	MS	MS	MS
87	Northward	0.1	N	N	3851.i	N	MS	MS	MS
2	MS	MS	MS	MS	MS	MS	North	N	North
61	MS	N	MS	North	N	N	Due north	North	North

Discussion

Our results suggest that hair is the most suitable biological matrix for evaluating systemic exposure of children to sympathomimetic amine stimulants, such as MAMP, AMP, and MDMA. More 60% of children with all 3 biological matrices had a positive hair result for at least one analyte. In contrast, only 18% and half dozen% had positive urine and OF tests, respectively. Low detection rates in OF and urine with positive hair tests in our study suggest drug exposure more than 1 calendar week prior to specimen collection, or environmental exposure. In a retrospective assay by Farst et al., 2011, the MAMP detection rate (82.2%) was higher in hair than urine (ii.2%) in samples from 45 children.¹⁵ Our study is the first to simultaneously compare drug concentrations in hair, urine and OF from drug-exposed children.

Typical immunoassay screening cutoffs are as well high to detect low drug concentrations in exposed children's urine and oral fluid specimens.^20-22 Testing, therefore, must be performed with lower cutoffs bachelor with mass spectrometric methods or loftier sensitivity ELISA assays. In addition, it is highly recommended that urine and/or OF samples are collected immediately after the kid is removed from the site of exposure.²⁹ This is to minimize faux negative results due to a narrow window of detection for MAMP, AMP and MDMA in urine and OF.

All 3 infants in our report tested positive for MAMP (0.27 – 4.5 ng/mg) with AMP (0.i ng/mg) or MDMA (0.1 – 0.25 ng/mg) in pilus; 1 likewise was positive for MAMP in OF (17.9 ng/mL) only had a negative urine test. This suggests more than contempo drug exposure. A source of MAMP exposure in immature children (infants and toddlers) could be from itch on floors and placing contaminated objects in their mouths. This besides was observed past Farst et al, who noted that children under 3 years of age were more than probable than older children (3 – 12 years old) to have a positive MAMP hair test, regardless of pilus colour.¹⁵ Based on our results, at that place is no significant departure in the likelihood of testing positive for MAMP between a child with blackness or brownish pilus and a child with blonde hair color (odds ratio 0.29, p-value 0.255). In another study, 52 hair samples were analyzed from children 2 months to xv years old recently removed from MAMP clandestine laboratories. Similarly, 73% of samples quantified >LOQ (0.i ng/mg) for MAMP, with children <five years erstwhile having the highest mean MAMP concentration (thirteen.8ng/mg) compared to the grouping mean (7.0ng/mg). No other biological specimens were analyzed from these children.^thirty Our lower mean MAMP concentration (3.3ng/mg)could exist attributed to the fact that children referred to CAARE were non all from MAMP secret laboratories, but from homes where the drug was allegedly consumed. All the same, finding drugs in our subjects'hair samples subsequently the incorporation of wash procedures in the analysis suggests environmental exposure. Another limitation we encountered was the anonymity of the children's historic period enrolled in the study due to active CPS custody cases during sample collection. Hence, we are non able to fully evaluate whether MAMP level in hair could come up from accidental and environmental exposure or self-assistants (adolescent MAMP consumption).

Han et al. reported that MAMP and AMP were detected in pilus samples (6 – twenty cm) from chronic adult MAMP users with concentration ranges of 0.39 - 35.2 ng/mg and 0.45 – 2.seven ng/mg for MAMP and AMP, respectively.²³ Participants self-reported insufflating ("snorting") or smoking 0.25 – four g/day MAMP. AMP/MAMP ratios of 0.08 - 0.32 were found in hair. When we orally administered four low (10 mg) and high (20 mg) doses South-(+)-MAMP HCl over 1 calendar week, incorporation of MAMP and AMP was dose-dependent.³¹ MAMP concentrations ranged from 0.six - 3.5 ng/mg after the low and 1.ii - 5.3 ng/mg subsequently the loftier dose. The study reported that the overall AMP/MAMP ratios ranged from 0.07 - 0.37 with a mean value of 0.15 ± 0.07. The median MAMP pilus concentration in the drug-exposed children in our report was 1.4ng/mg with AMP/MAMP ratios of 0.02 - 0.12.This would suggest a systemic ingestion of the drug.

The boilerplate hair growth in adults is 1 cm/month^32-33, while pilus growth in children varies more than and is proportional to the duration of the growing anagen stage.³⁴ Biological factors such equally diet, illness, metabolic disorders or stages in a child'due south development can likewise influence hair growth.³⁴ Assessment of the magnitude and duration of a child's drug exposure through pilus analysis should be washed cautiously for these reasons.

Children are uniquely susceptible to a myriad of harmful effects from their MAMP-using caregivers. These include the possibility of direct MAMP exposure through contaminated surfaces ³⁵, directly ingestion, physical abuse and neglect by caregivers (or their associates). There besides is an increased take a chance of exposure to crime, hypersexuality, intimate partner and interpersonal violence in the dwelling house.

Cases of children exposed to acutely loftier MAMP levels via direct ingestion involved CNS excitation, tachycardia, rhabdomyolysis, and hyperthermia.^{16, 36-37} Infants and toddlers living in MAMP homes are at higher risks due to their smaller size, faster metabolism, prolonged indoor exposure, and propensity to crawl and place objects in their mouths. Direct pare exposure and contact with MAMP was documented³⁸, although, effects of chronic low dose MAMP exposure in children are not well described. Serious detrimental furnishings on children's health and welfare from such living environments are well-documented.^{xiii, 17, 39-40}

Parents preoccupied with drug use (or abuse) have significant difficulties forming healthy emotional attachments with their children that are disquisitional for normal babyhood development. Early on interventions such every bit immediate removal from contaminated areas, medical handling and counseling are necessary to help drug-endangered children from short- and long-term furnishings of MAMP exposure.

Conclusion

These are the first data of which we are aware comparison concurrently collected hair, OF, and urine specimens from children with MAMP ecology exposures. Drug exposure from possible ecology contamination in children is typically evaluated with conventional urine drug testing. Pilus analysis was shown to be a more sensitive method than urine in evaluating environmental drug exposure in children.^{15, thirty, 41} Yet, other sources of MAMP exposure could exist self-administration in adolescents, and ingestion in toddlers exposed to MAMP from solid material on floors or surfaces. Higher MAMP detection rates in hair than OF and urine in our data suggest that pilus testing is a valuable tool for identifying drug-exposed children. Hair testing offers a wider window of detection for identifying MAMP-, AMP-, and MDMA-exposed children than OF or urine. A negative drug test in urine, OF or pilus does non ensure the absence of drug exposure, simply hair testing provides the best opportunity for identifying children exposed to MAMP, AMP and MDMA in their surround.

Acknowledgments

The authors admit the contributions of the staff of the Intramural Research Program, National Institutes of Health, National Plant on Drug Abuse (NIDA/IRP),the Academy of California, Davis, equally well every bit the Graduate Partnership Program. Psychemedics, Corporation provided hair testing and results. This enquiry was supported and funded past the Intramural Inquiry Programme, National Institutes on Drug Abuse and National Institutes of Health.

Supported by: Intramural Research Program, National Institutes on Drug Abuse and National Institutes of Health, University of California, Davis, Psychemedics, Corporation (pilus testing and results)

Funded by: Intramural Research Plan, National Institutes on Drug Abuse and National Institutes of Health.

Footnotes

The authors alleged no conflict of interest.

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