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2.
Clin Biochem ; 76: 38-41, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31809697

RESUMO

During the routine validation of a benzodiazepine method (performed on a Liquid Chromatography - Tandem Mass Spectrometer), it was noted that lorazepam, triazolam, and α-hydroxytriazolam showed a quadratic shift/bias in the calibration curve, particularly at high concentrations. The ultimate cause of this bias was determined to be due to the natural presence of chlorine (Cl) isotopes (35Cl and 37Cl) in these benzodiazepines. The presence of the heavy (37Cl) isoforms of Cl resulted in the analyte's mass being the same as the internal standard which, in turn, caused the internal standard to appear "falsely increased", thus skewing the calibration curve. One solution to this potential issue was to take advantage of this natural phenomenon and use the Cl heavy isoforms of the respectively labeled internal standards.


Assuntos
Benzodiazepinas/sangue , Cloro/química , Calibragem , Cromatografia Líquida , Humanos , Padrões de Referência , Espectrometria de Massas em Tandem
3.
Environ Pollut ; 254(Pt B): 113049, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31454582

RESUMO

This study aimed to determine if there is a co-elevation of human blood arsenic and mercury levels in the Midwestern population of the United States (U.S.) and to determine any geographical patterns and variation of arsenic and mercury that may exist in Michigan. 58,800 blood specimens along with associated demographic/geographic data from the contiguous United States were reviewed. Univariate and multivariable logistic regression were used to analyze demographic/geographic variables associated with elevated arsenic concentrations. Furthermore, blood data from patients in Michigan were aggregated to the ZIP code tabulation area (ZCTA) in order to assess geographic variation using spatial regression models. SaTScan software was also used to analyze potential clustering of arsenic and mercury across Michigan ZCTAs. Within the contiguous United States, elevated mercury blood concentrations, older age, female sex, and coastal status were all associated with elevated arsenic blood concentrations (elevated mercury odds ratio (OR) 3.18 (3.04-3.33); female sex OR 1.06 (1.02-1.11); +10 yr age OR 1.12 (1.11-1.14); coastal state OR 1.33 (1.27-1.40). Within the state of Michigan, as with the continuous U.S., elevated mercury blood concentrations and older age were associated with elevated arsenic blood concentrations (elevated mercury OR 2.75 (2.38-3.18); female sex OR 1.06 (0.95-1.19); +10 yr age OR 1.10 (1.06-1.13). Using spatial regression, it was determined that within Michigan, economic inequality (measured via the Gini coefficient) was also associated with elevated concentrations of mercury in the blood. Clinical reference laboratory data, in conjunction with spatial analysis methods, may enhance our understanding of how elemental exposure affects human health and should be considered for studying how environmental contaminants, socioeconomics and geography affect the health of populations.


Assuntos
Arsênico/análise , Exposição Ambiental/análise , Mercúrio/análise , Adulto , Idoso , Exposição Ambiental/estatística & dados numéricos , Feminino , Geografia , Humanos , Masculino , Michigan , Pessoa de Meia-Idade , Estados Unidos
4.
JPEN J Parenter Enteral Nutr ; 43(8): 970-976, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31197862

RESUMO

BACKGROUND: Trace-element contamination of contemporary parenteral nutrition (PN) components exists in unknown quantities and, in combination with excessive amounts of certain trace elements provided in commercially available adult, pediatric, and neonatal multitrace-element (MTE) products, could result in eventual accumulation and toxicity. This study aims to quantify trace-element contamination in components used for PN compounding to further inform recommendations for MTE product reformulation and individualized trace-element prescribing in PN. METHODS: A total of 32 unique components (65 products) available for PN compounding were tested for manganese, chromium, selenium, zinc, and copper contamination, utilizing inductively coupled plasma mass spectrometry. Theoretical adult, pediatric, and neonatal PNs were formulated to assess the impact of macronutrient and micronutrient component doses on PN trace-element contamination. RESULTS: Trace-element contamination was detected in 24 (75%) components tested. Chromium and manganese were common, present in 65.6% and 51.5% of all components, respectively. Eight components did not contain detectable trace-element contamination, most notably sterile water, concentrated dextrose, and lipid emulsion. Manganese contamination in theoretical adult, pediatric, and neonatal PN was 25.18, 9.92, and 1.37 µg, respectively. Chromium contamination was 4.85, 1.5, and 0.28 µg, respectively. CONCLUSION: Trace-element contamination was prevalent in components used to compound PN. Our findings support reformulation of adult, pediatric, and neonatal manufactured MTE products to eliminate chromium, decrease manganese, and supply full daily physiologic requirements of selenium, zinc, and copper. Future study is needed to assess the additional contamination that could occur through the compounding and storage processes.

8.
Urology ; 126: 49-53, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30654140

RESUMO

OBJECTIVE: To further analyze calcium tartrate tetrahydrate stones after a recent case report described this novel stone. Prior to this, there was only one previously reported occurrence of this stone in a human. This unusual stone composition is not tested for routinely. True prevalence and possible causes of this stone are unknown. MATERIALS/METHODS: During the previous case report, micro-CT and Fourier-transform infrared spectroscopy were used to identify a calcium tartrate tetrahydrate stone. This information was applied to urinary stones with previously unidentified compositions in the Mayo Metals laboratory database between 2010 and March 2018. Two additional stones were identified at our institution. Three patients had medical records available for analysis. RESULTS: Between 2010 and March 2018, 35 calcium tartrate stones in 25 patients were identified in the Mayo database as well as 2 at our institution (37 stones in 27 patients). Thirty stones were pure calcium tartrate with the remainder having elements of more common stones. The average age was 46.3 (±14.7) with a slightly higher incidence in females (17 vs 10). Of the 3 medical records investigated, all 3 were males (average age 48.7), and each reported consumption of an energy supplement (Spark) routinely. CONCLUSION: The true prevalence of this relatively unknown stone remains unclear and additional investigation is warranted. We believe all stone laboratories should have access to the IR spectra for calcium tartrate tetrahydrate. Attention should be paid to possible causes of this stone, particularly with relation to oral supplements, to aid with future prevention and treatment.


Assuntos
Tartaratos/análise , Cálculos Urinários/química , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Espectroscopia de Infravermelho com Transformada de Fourier , Adulto Jovem
10.
Artigo em Inglês | MEDLINE | ID: mdl-30602515

RESUMO

The clinical utility of ganciclovir therapeutic drug monitoring (TDM) is unknown. We retrospectively analyzed adult patients treated for cytomegalovirus (CMV) infection with ganciclovir with TDM between 2005 and 2015. The primary outcome was an association between ganciclovir TDM and clinical efficacy endpoints within 30 days, defined by viral load and symptomatology. Secondary outcomes included safety endpoints, evaluated within 7 days of the last administered dose of ganciclovir. Of 175 patients evaluated, 82 patients with CMV infection were included in our analysis with a median (interquartile range) baseline CMV viral load of 5,500 (3,000 to 15,200) copies/ml. The majority achieved undetectable or reduced CMV viral load below the lower limit of quantification (74.4%) with improvement in symptomatology (70.7%) at 30 days. Among patients with detectable CMV viremia at 30 days, the viral load had declined to a median of 1,000 (1,000 to 3,090) copies/ml. We did not observe significant associations between the efficacy outcomes and ganciclovir trough (P = 0.20 and P = 0.20, respectively) or peak concentrations (P = 0.14 and P = 0.14, respectively). Similarly, there was no significant association between ganciclovir trough or peak concentrations and safety endpoints, including leukopenia (P = 0.48 and P = 0.69), neutropenia (P = 0.59 and P = 0.69), thrombocytopenia (P = 0.29 and P = 0.37), anemia (P = 0.51 and P = 0.35), nephrotoxicity (P = 0.41 and P = 0.57), and neurotoxicity (P = 0.22 and P = 0.48). We did not observe any associations between ganciclovir TDM and clinical efficacy or safety endpoints. Routine ganciclovir TDM may be of limited value. Future studies may be warranted to identify specific populations with unpredictable pharmacokinetic and pharmacodynamics profiles in whom ganciclovir TDM may be of benefit.


Assuntos
Antivirais/uso terapêutico , Infecções por Citomegalovirus/tratamento farmacológico , Citomegalovirus/efeitos dos fármacos , Ganciclovir/uso terapêutico , Carga Viral/efeitos dos fármacos , Antivirais/efeitos adversos , Antivirais/farmacocinética , Monitoramento de Medicamentos , Feminino , Ganciclovir/efeitos adversos , Ganciclovir/farmacocinética , Humanos , Masculino , Pessoa de Meia-Idade , Segurança do Paciente , Estudos Retrospectivos , Resultado do Tratamento
11.
Methods Mol Biol ; 1872: 41-50, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30350277

RESUMO

The use and adherence monitoring of opioids in pain management is recommended by numerous clinical practice guidelines. Many physicians use urine immunoassay screening tests, which suffer from a lack of sensitivity and specificity, to verify compliance to pain medications. However, several immunoassay tests are required to comprehensively detect the synthetic, semisynthetic, and natural opioids due to the limited cross-reactivity of each assay. Superior testing strategies are required to specifically identify low concentrations of opioids found in adherent pain management patients. Therefore we present a method for the qualitative identification of 33 opioids and metabolites (codeine, codeine-6-ß-glucuronide, morphine, morphine-6-ß-glucuronide, 6-acetylmorphine, hydrocodone, norhydrocodone, dihydrocodeine, hydromorphone, hydromorphone-3-ß-glucuronide, oxycodone, noroxycodone, oxymorphone, oxymorphone-3-ß-glucuronide, noroxymorphone, meperidine, normeperidine, methadone, EDDP, propoxyphene, norpropoxyphene, tramadol, O-desmethyltramadol, tapentadol, tapentadol-ß-glucuronide, N-desmethyltapentadol, buprenorphine, norbuprenorphine, norbuprenorphine glucuronide, naloxone, naloxone glucuronide, fentanyl, and norfentanyl) in unhydrolyzed urine using a liquid chromatography tandem mass spectrometry (LC-MS/MS) with high-resolution, accurate-mass Orbitrap detection.


Assuntos
Analgésicos Opioides/farmacocinética , Cromatografia Líquida , Detecção do Abuso de Substâncias , Espectrometria de Massas em Tandem , Analgésicos Opioides/uso terapêutico , Cromatografia Líquida/métodos , Humanos , Manejo da Dor , Detecção do Abuso de Substâncias/métodos , Espectrometria de Massas em Tandem/métodos
12.
Methods Mol Biol ; 1872: 111-118, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30350284

RESUMO

Numerous methods for the measurement of tacrolimus and cyclosporine A involving traditional liquid chromatography tandem mass spectrometry (LC-MS/MS) have previously been described. The majority of these methods use solid-phase extraction, liquid-liquid extraction, or protein precipitation extraction with instrument run times greater than 15 s per sample. Continued demands in clinical labs for greater efficiency and throughput have put increased stress on traditional technologies such as high-performance liquid chromatography-ultraviolet detection (HPLC-UV) and traditional LC-MS/MS. As an improvement to the existing methods, we describe a sensitive ultrafast LC-MS/MS with run times of less than 15 s per sample.


Assuntos
Cromatografia Líquida , Ciclosporina/farmacocinética , Monitoramento de Medicamentos , Tacrolimo/farmacocinética , Espectrometria de Massas em Tandem , Monitoramento de Medicamentos/métodos
13.
Clin Chem ; 65(2): 242-253, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30305277

RESUMO

BACKGROUND: Since 2013, an unprecedented surge in fentanyl overdose deaths has been caused by heroin laced with illicitly produced fentanyl and/or fentanyl analogs (FAs) sold as heroin. The US Drug Enforcement Agency's National Forensic Laboratory Information System reported a >300% increase in fentanyl encounters from 4697 in 2014 to 14440 in 2015. In 2015, the CDC reported 9580 deaths caused by synthetic opioids, primarily fentanyl, a 72% increase from 2014. The European Monitoring Centre for Drugs and Drug Addiction has also encountered several new FAs in the heroin supply. Counterfeit pharmaceuticals containing mixtures of fentanyl and FAs continue to be a poorly recognized worldwide problem despite the WHO classifying several FAs as a serious threat to public health. CONTENT: This review covers the epidemiology of fentanyl abuse and discusses the clinical practice implications of widespread fentanyl abuse. It includes a historical perspective on the illicit FAs that have appeared in the US and European Union and reviews the methods available to identify FAs and emerging technologies useful for identifying previously undescribed analogs. A compilation of structural and mass spectral data on FAs reported thus far is provided. SUMMARY: Fentanyl and FAs have evolved into a global public health threat. It is important to understand the analytical, clinical, and regulatory efforts underway to assist communities affected by the current fentanyl epidemic.


Assuntos
Analgésicos Opioides/administração & dosagem , Fentanila/administração & dosagem , Transtornos Relacionados ao Uso de Substâncias/patologia , Analgésicos Opioides/efeitos adversos , Analgésicos Opioides/análise , Europa (Continente)/epidemiologia , Fentanila/efeitos adversos , Fentanila/análogos & derivados , Humanos , Insuficiência Respiratória/etiologia , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/mortalidade , Estados Unidos/epidemiologia
14.
Clin Biochem ; 65: 53-54, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30578759

RESUMO

A 35-month-old female with nonketotic hyperglycinemia (NKH) presented to the Emergency department with severe hypoglycemia, fever, and several episodes of seizures. Due to worsening respiratory status, additional seizures and anion gap worsening metabolic acidosis the patient was transferred to the pediatric intensive care unit. The useful mnemonics for causes of high anion gap metabolic acidosis are the classic MUDPILES (representing Methanol, Uraemia, Diabetes, Paraldehyde, Iron (and Isoniazid), Lactate, Ethylene glycol, and Salicylate) and the more recently proposed GOLD MARK (Glycols [ethylene and propylene], Oxoproline, l-lactate, d-lactate, Methanol, Aspirin, Renal failure, and Ketoacidosis) as causes of the anion gap metabolic acidosis were all ruled out. Relatively stable concentrations of salicylate (approximately 10 mg/dL, 0.7 mmol/L) were noted, despite no evidence the patient received aspirin Therefore further laboratory testing was performed. A Basic-Acid-Neutral (BAN) gas chromatography mass-spectroscopy (GC-MS) Drug screen of urine was undertaken. A large benzoic acid peak was identified by spectral match, which supported the clinical history that the patient was taking sodium benzoate powder 1175 mg as a dietary supplement three times a day. However, salicylate was not identified. This patient had benzoic acid concentration in excess of 2000 µg/mL. Given that benzoic acid is a weak acid, with a pK of approximately 4 it is almost completely ionized at pH 7. Therefore, the large amount of benzoic acid was not only thought to be contributing to the patient's anion gap metabolic acidosis, but the source of the interference in the salicylate assay.


Assuntos
Acidose/metabolismo , Equilíbrio Ácido-Base/fisiologia , Ácido Benzoico/metabolismo , Pré-Escolar , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Humanos
16.
Clin Rheumatol ; 37(10): 2685-2692, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30014357

RESUMO

The aim of this study is to evaluate the relationship between baseline serum 25-hydroxyvitamin D3 levels and SLE activity/flares over time. This is a longitudinal study of 276 patients who fulfilled ≥ 4 ACR criteria for SLE and recruited in the year 2011. Serum samples were collected at baseline and assayed for 25-hydroxyvitamin D3 at the end of a mean follow-up of 32.5 months. Participants were stratified into three groups according to baseline 25-hydroxyvitamin D3 levels: group I (< 15 ng/ml, deficiency), group II (15-30 ng/ml, insufficiency), and group III (> 30 ng/ml, adequate). Baseline and summated SLE disease activity index (SLEDAI) score over time and the annual incidence of lupus flares were compared among these groups. 25-hydroxyvitamin D3 levels of < 15, 15-30, and > 30 ng/ml were present in 26, 54, and 20% of the recruited patients, respectively. Group I had significantly higher baseline SLEDAI scores. After a follow-up of 32.5 ± 5.5 months, 153 mild/moderate and 91 severe flares developed. The mean summated SLEDAI was 3.2 ± 2.0 in group I, 2.4 ± 1.9 in group II and 2.7 ± 2.1 in group III patients (P = 0.02). The annual incidence of mild/moderate and severe flares was 0.26 ± 0.39 and 0.20 ± 0.45 (group I); 0.20 ± 0.33 and 0.09 ± 0.22 (group II); and 0.20 ± 0.32 and 0.14 ± 0.46 (group III), respectively (P > 0.05). In a subgroup of 73 patients who were clinically and serologically quiescent at baseline, a similar trend of more flares was observed in group I patients. Vitamin D deficiency was frequent in Chinese SLE patients and was associated with more active disease at baseline and over time, as well as a trend of more severe lupus flares.


Assuntos
Calcifediol/sangue , Lúpus Eritematoso Sistêmico/sangue , Exacerbação dos Sintomas , Adulto , Feminino , Humanos , Hidroxicloroquina , Estudos Longitudinais , Masculino , Índice de Gravidade de Doença , Deficiência de Vitamina D
17.
Radiology ; 288(2): 416-423, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29737947

RESUMO

Purpose To determine whether gadolinium accumulates within cerebrospinal fluid (CSF) in patients recently exposed to the macrocyclic agent gadobutrol and identify factors that may affect this accumulation. Materials and Methods In this prospective observational cohort study, gadolinium was quantified by using inductively coupled plasma mass spectrometry of CSF samples from patients who underwent gadobutrol-enhanced magnetic resonance (MR) imaging followed by lumbar puncture within 30 days (gadobutrol group) or patients who underwent lumbar puncture without history of gadolinium-enhanced MR imaging (control group). CSF total protein level of 35 mg/dL or lower was used as a surrogate marker of an intact blood-brain barrier (BBB). Associations between gadolinium CSF concentration and patient characteristics were examined by using log (e)-linear regression models. Results A total of 82 patients (68 in gadobutrol group, 14 in control group; 42 male and 40 female patients; median age, 47 years [interquartile range, 25-65 years]) were included in this study. Gadolinium was detected in the CSF of all 68 patients in the gadobutrol group (100% [95% confidence interval: 94.7, 100]; range, 0.2-1494 ng/mL). CSF total protein level higher than 35 mg/dL and patient age of at least 18 years were associated with higher gadolinium concentrations (estimate: 1.1, with standard error [SE] of 0.26 [P < .001] and 0.91, with SE of 0.37 [P = .02], respectively). Conclusion Intravenous administration of the macrocyclic agent gadobutrol results in gadolinium accumulation within the CSF, even in the setting of normal renal function and no BBB dysfunction.


Assuntos
Meios de Contraste/farmacocinética , Aumento da Imagem/métodos , Imagem por Ressonância Magnética/métodos , Compostos Organometálicos/líquido cefalorraquidiano , Compostos Organometálicos/farmacocinética , Adulto , Idoso , Estudos de Coortes , Feminino , Gadolínio/líquido cefalorraquidiano , Gadolínio/farmacocinética , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Espectrofotometria Atômica/métodos , Punção Espinal
18.
Clin Biochem ; 58: 125-127, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29802836

RESUMO

OBJECTIVE: False-positive urine drug of abuse screening (UDS) results can have serious implications in clinical practice, particularly when confirmation assay results are not immediately available to providers making medical decisions. Often it is not possible to identify the specific medication or other interfering compound that is responsible for the false-positive UDS result. Even when a potential interference is reported in the literature or package insert for one assay, the applicability to other UDS platforms/assays is often unknown. Mexiletine has been suggested as a cause of false-positive amphetamine results, but never confirmed as the causative agent in previous reports. The goal of this study was to confirm this drug as a cross-reacting compound in amphetamine screening tests. METHODS: We evaluated several amphetamine screening assays: the Syva EMIT II Plus and the Roche KIMS automated immunoassays, along with the Noble Split-Specimen and Synchron QuikScreen point-of-care assays. RESULTS: Urine samples from two patients treated with mexiletine were positive on all amphetamine screens but confirmed negative by mass spectrometry. Drug-free urine spiked with mexiletine caused positive results on all assays, although the EMIT II Plus and KIMS assays cross-reacted at lower mexiletine concentrations than the point-of-care assays. CONCLUSION: This report confirms that mexiletine can cross-react on several amphetamine screening assays. Assay manufacturers are encouraged to evaluate mexiletine cross-reactivity, and providers and laboratories should be aware of the potential for false-positive amphetamine screening results in patients taking mexiletine.


Assuntos
Transtornos Relacionados ao Uso de Anfetaminas/urina , Anfetamina/urina , Mexiletina/administração & dosagem , Reações Falso-Positivas , Feminino , Humanos , Imunoensaio/instrumentação , Imunoensaio/métodos , Masculino
20.
Clin Chem ; 63(12): 1810-1811, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29184039
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