Anal. Chem. 1999, 71, 309R-313R
Capillary Electrophoresis Yan Xu
Department of Chemistry, Cleveland State University, Cleveland, Ohio 44115 This review covers the clinical chemistry applications of capillary electrophoresis published during the period of October 1996 to October 1998. The search method for the literature has
been CA Selects for Capillary Electrophoresis from the Chemical Abstracts Service. Athough the implementation of CE methods in routine clinical laboratories has been slow, there has been a
Table 1. Analyses of Drugs and Their Metabolites by CE drugs or metabolites abuse drugs cocaine, 3,4-methylenedioxymethamphetamine, morphine D-lysergic acid diethylamide anticancer drugs idarubicin, idarubicinol tamoxifen, N-desmethyltamoxifen, 4-hydroxytamoxifen anti-infective agents amikacin cefotaxime and its deacetyl metabolite cefuroxime cephalosporins cephalosporins ciprofloxacin, desethyleneciprofloxacin antiinflammatory and immunomodulating agents acetaminophen, salicylic acid acetaminophen, salicylic acid, sulfamethoxazole, tolbutamide, trimethoprim arpromidine-type histamine H2-receptor agonist aspirin metabolites dimethindene and its metabolites ibuprofen and its major phase I metabolites ketoprofen cardiovascular drugs amiloride, triamterine, bendroflumethiazide, bumetanide amlodipine enantiomers atenolol procainamide, N-acetylprocainamide warfarin enantiomers central nervous system drugs barbiturates barbiturates, benzodiazepines, methaqualone, thiodiphenylamines lamotrigine methadone and its main metabolite methaqualone mianserin and its metabolites ondasetron enantiomers pentazocine enantiomers pentobarbital enantiomers prolintane, oxoprolintane secobarbital enantiomers sufentanil triazolam, flunitrazepam, nitrazepam endocrine system drugs pseudooligosaccharide acarbose and its main metabolite sulfonylurea peripheral nervous system drugs amphetamine mepivacaine enantiomers methamphetamine phenethylamines piracetam prilocaine enantiomers tacrine, 7-methoxytacrine, and their basic metabolites respiratory drugs ambroxol, bromhexine dexamethasone theophylline theophylline and its metabolites 10.1021/a1999903u CCC: $18.00 Published on Web 05/20/1999
© 1999 American Chemical Society
sample matrixes
CE modes
refs
hair blood
CZE CZE
C1 C2, C3
plasma serum
CZE CZE
C4 C5
plasma plasma serum urine, bile plasma plasma
MECC CZE/MECC MECC CZE CZE CZE
C6 C7 C8 C9 C10 C11
plasma plasma urine urine, plasma urine urine serum
MECC MECC CZE MECC CZE CZE CZE
C12 C13 C14 C15 C16 C17 C18
urine plasma urine urine serum
CZE CZE CZE CZE CZE
C19 C20 C21 C22 C23
plasma, urine plasma, urine, gastric juice serum urine, serum, hair urine, blood plasma serum serum serum urine serum plasma urine
MECC/CZE MECC/CZE CZE CZE MECC CZE CZE CZE CZE CZE CZE CZE MECC
C24, C25 C26 C27 C28-C30 C31 C32 C33 C34 C35 C36 C37 C38 C39
urine urine
CZE MECC
C40 C41
urine serum urine urine plasma serum urine, serum
CZE CZE CZE CZE CZE CZE CZE
C42 C43 C44 C45 C46 C47 C48
urine, blood tears serum plasma, saliva, urine
CZE CZE microchip CE CZE
C49 C50 C51 C52
Analytical Chemistry, Vol. 71, No. 12, June 15, 1999 309R
Table 2. Analyses of DNA and RNA by CE applications genetic diseases aldehyde dehydrogenase 2 genotype angiotensin-converting enzyme gene apolipoprotein B gene apolipoprotein B-100 gene apolipoprotein E gene atherosclerosis bladder cancer breast cancer breast tumor colorectal cancers deafness susceptibility genes Duchenne/Becker muscular dystrophy factor V Leiden FcER1β IgE gene fetal alloimmunization fragile X syndrome hemochromatosis hemochromatosis 21-hydroxylase deficiency Leber’s hereditary optic neuropathy lymphoproliferative disorders methylenetetrahydrofolate reductase gene P-53 gene thalassemias virology cytomegalovirus DNA hepatitis B virus DNA hepatitis C virus herpes simplex virus, hepatitis C virus HIV-1RNA forensic analyses mitochondrial DNA STR locus D1S8 STR locus D1S80 STR locus HUMACTBP2 STR locus HUMCD4 STR loci HUMCD4, HUMTH01, HUMD21S11, HUMSE33 STR loci HUMTH01, HUMF13A1, HUMFES/FPS X-Y homologous amelogenin gene
methods
refs
PCR PCR PCR/VNTR PCR/point mutation PCR/RFLP RT-PCR/bFGF-mRNA PCR/STR RT-PCR/mRNA differential display competitive PCR/estrogen receptor mRNA PCR/TGF-β type II receptor gene CAE/multiplex PCR/CA repeat markers multiplex PCR PCR/point mutation PCR/CA repeat PCR/Rh D/d genotyping PCR/CGG repeats PCR/Cys282Tyr mutation CAE chips/HLA-H DNA PCR/ARMS ligase chain reaction/point mutation PCR/T-cell gene rearrangement PCR/C677T mutation PCR/SSCP/point mutation PCR/point mutation
C53 C54 C55 C56 C57-C60 C61 C62 C63 C64 C65 C66 C67, C68 C69 C70 C71 C72 C73 C74 C75 C76 C77 C78, C79 C80, C81 C82
competitive PCR PCR/SSCP RT-PCR RT-PCR DNA probe
C83 C84 C85 C86 C87
PCR/RFLP PCR multiplex PCR PCR PCR PCR PCR PCR
C88 C89 C90 C91 C92 C93 C94 C95
Table 3. Analyses of Proteins by CE proteins cerebrospinal fluid β2-microglobulin, γ-trace protein, myelin basic protein, R1-acid glycoprotein β-trace protein serum globulins lipoproteins paraproteins platelet membrane glycoprotein IIb-IIIa complex urine R1-acid glycoprotein, Tamm Horsfall albumin, Bence Jones, γ, Tamma Hall, transferrin Bence Jones, intact Ig, Tamm Horsfall
diseases
CE modes
refs
central nervous system disease central nervous system disease
CGE CGE
C96 C97
various diseases (e.g., inter alia inflammation, nephrotic syndrome, polyclonal gammopathy) cardiovascular disease
CZE
C98-C103 C104-C108
dysproteinemia, paraproteinemia Glanzmann thrombasthenia
CZE/MECC/ CITP CZE CZE
C109, C110 C111
diabetic nephropathy renal disorders, light-chain disease glomerular proteinuria
MECC CZE CZE
C112 C113 C114
Table 4. Diagnosis of Metabolic Disorders by CE metabolic disorders adenylosuccinase deficiency, 5-oxoprolinuria, propionic acidemia, HHH syndrome Addison’s disease, Cushing’s syndrome, hirsutism and virilism, adrenal adenomas, hypertension, congenital adrenal hyperplasia alkaptonuria, neuroblastoma, galactosemia carbohydrate-deficient glycoprotein syndrome glyceric aciduria, lysinuric protein intolerance, methylmalonic aciduria hypoxia long-chain fatty acids neuropsychiatric disorders orotic aciduria prolidase deficiency thyroid function unusual metabolic situations of immature newborns 310R
Analytical Chemistry, Vol. 71, No. 12, June 15, 1999
sample matrixes
CE modes
refs
urine urine, serum
CZE MECC
C115 C116
urine serum urine serum plasma cerebrospinal fluid urine urine serum umbilical blood
CZE CZE/CGE CZE CZE MECC CZE CZE CZE CZE CZE
C117 C118-C120 C121 C122 C123 C124 C125, C126 C127, C128 C129 C130
Table 5. Enzyme Activity Assays by CE enzymes
analytes
sample matrixes
CE modes
N-acetyltransferase N-acetyltransferase 1 N-acetyl-β-glucosaminidase cytochrome P 4501A2 β-glucuronidase γ-glutamyl hydrolase prolidase purine nucleoside phosphorylase
5-(acetylamino)-6-(formylamino)-3-methyluracil/1-methylxanthine p-aminosalicylic acid (PAS)/N-acetyl-PAS 4-methylumbelliferone 1,7-dimethylxanthine/1,3,7-trimethylxanthine 4-methylumbelliferone methotrexate Gly-Pro, Leu-Pro, Ala-Pro hypoxanthine
urine urine urine urine urine eukaryotic cells skin fibroblast erythrocytes
MECC CZE CZE MECC CZE CZE CZE CZE
refs C131 C132 C133 C131 C134 C135 C136 C137
Table 6. Analyses of Inorganic Ions and Small Organic Molecules by CE analytes inorganic ions Cu, Pb K nitrate nitrite, nitrate Zn, Cu, Cd, Co, Fe, Cr, Mn, Ca, Ni, Mg Fe uranyl phosphates markers of glomerular filtration rate iothalamate meglumine iohexol, iothalamate modified bases of nucleic acids pseudouridine nucleotides 8-hydroxydeoxyguanosine guanine organic acids amino acids L-ascorbic acid creatinine creatinine, vanylmandelic acid, homovanillic acid, uric acid creatinine, other uremic toxins formic acid glutamate, aspartate homocysteine, glutathione, cysteine lactate, pyruvate, other organic acids methylmalonic acid muconic acid salicylic acid short-chain organic acids tryptophan and its metabolites uric acid peptides insulin neuropeptides steroids cortisol corticosteroid hormones sugars glucose glucose, galactose
sample matrixes
CE modes
refs
serum vitreous humor serum, cerebrospinal fluid, urine, tissue plasma serum protein serum serum
CZE CZE CZE CZE CZE CZE CZE
C138 C139 C140 C141 C142 C143 C144
urine, plasma serum
CZE CZE
C145 C146
urine
MECC/CZE
C147, C148
hematopoietic cells urine
CZE CZE
C149 C150
urine serum, urine, stomach fluid urine urine serum urine brain microdialyzate plasma neonatal urine serum urine serum, urine urine urine urine, plasma
CZE CITP/CZE CZE MECC MECC CZE CZE CZE CZE CZE CZE CZE CZE CZE CZE
C151 C152 C153, C154 C155 C156 C157 C158 C159 C160 C161 C162 C163, C164 C165 C166 C167, C168
pancreatic tissue plasma
CZE CZE
C169 C170
urine serum
MECC MECC
C171 C172
tear urine
CZE CZE
C173 C174
rapid expansion of CE in clinically related research. This review is not intended to provide readers a detailed description of the published papers; rather, the author has tried to summarize the important research activities in clinical chemistry into several categories (Tables 1-6). The author feels that he may give a fair coverage to a variety of clinical chemistry applications, while allowing the readers to search for a specific application and get to its original publications quickly. Yan Xu is an associate professor of the Chemistry Department at Cleveland State University. He received his B.S. degree in chemistry from Zhongshan University (PRC) in 1982. He worked as a research chemist in China for three years before attending graduate school in the United States. He received a M.S. degree in chemistry from California State University, Fresno, in 1987, and a Ph.D. degree in analytical chemistry from the University of Cincinnati in 1991. Dr. Xu is presently the Head of the Analytical Chemistry Division in the Department of Chemistry at CSU. He has authored more than 70 scientific publications and presentations. His research interests include the development of novel analytical techniques for biomedical, clinical, and pharmacological analyses using immunochemical, capillary electrophoretic, chromatographic, mass spectrometric, and electroanalytical techniques.
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