血浆中辅酶Q10和羟乙基淀粉定量分析方法研究和应用
|
摘要
1.血浆中辅酶Q10定量分析方法研究和应用
背景辅酶Q10是人体能自身合成的脂类物质,是线粒体呼吸链的辅因子,具有抗氧化作用。它极性较弱,体内本底浓度较高。
目的建立专属、易操作的液相色谱-串联质谱法,测定人血浆中的辅酶Q10,并用于辅酶Q10的生物等效性研究。
方法LC-MS/MS法测定人血浆中的辅酶Q10。血浆样品经正己烷液-液萃取两次,以甲醇为流动相,Capcell Pak C18柱(35 mm×2.0 mm I.D.,5μm)进行分离,采用大气压化学电离源,以多反应监测(MRM)方式进行正离子检测。用于定量分析的离子反应分别为m/z 864→m/z 197(辅酶Q10)和m/z 796→m/z 197(内标辅酶Q9)。
结果测定血浆中辅酶Q10的线性范围为10.0 ~ 1000 ng?mL-1,定量下限可达10.0 ng?mL-1,日内、日间精密度(RSD)均小于8.9%,准确度(RE)在-0.9% ~ 3.8%之间。单个样品分析时间为4.5 min。
结论本文所建立的液相色谱-串联质谱法灵敏,专属,快速,适用于辅酶Q10的血药浓度测定及其生物等效性评价。
2.血浆和尿中羟乙基淀粉定量分析方法研究和应用
背景羟乙基淀粉是由不同链长度和不同羟乙基取代位点的葡萄糖多聚体组成。它作为代血浆,临床上主要用于补充血容量不足。在羟乙基淀粉浓度测定时,需要将其水解为单体,通过测定葡萄糖单体浓度,从而计算羟乙基淀粉浓度。因此,在其浓度测定时,需排除内源性本底浓度的干扰,建立灵敏、专属的分析方法。
目的建立灵敏、专属的定量分析方法,测定人血浆和尿中的羟乙基淀粉,并用于羟乙基淀粉200/0.5的人体药代动力学研究。
方法己糖激酶法间接测定人血浆和尿样中的羟乙基淀粉。血浆和尿样先用三氯乙酸沉淀去除血浆蛋白,再用丙酮沉淀上清液中的羟乙基淀粉,最后,用三氟乙酸(油浴1.5 h,100°C)水解,采用己糖激酶法进行测定,从而计算人血浆和尿样中的羟乙基淀粉。
结果测定血浆和尿中羟乙基淀粉的线性范围均为0.250 ~ 10.0 mg?mL-1,定量下限均为0.25 mg?mL-1;测定血浆中羟乙基淀粉的日内、日间精密度(RSD)均小于13.2%,准确度(RE)在-2.0% ~ -0.7%之间;测定尿中羟乙基淀粉的日内精密度小于4.8%,准确度(RE)在-3.9% ~ -1.2%之间。平均8 min能测定50个经预处理后的样品。
结论本文所建立的己糖激酶法灵敏,快速,已成功用于羟乙基淀粉200/0.5注射液的临床药代动力学研究。
1. Quantitative analysis of coenzyme Q10 in human plasma and its applications
Background Coenzyme Q10 (CoQ10) is an endogenous enzyme cofactor that exsits in all living cells in humans. It is an electron carrier in the mitochondrial respiratory chain and act as a lipid-soluble antioxidant.
Objective To develop and validate a specific and rapid liquid chromatographic?tandem mass spectrometric method for determination of coenzyme Q10 in human plasma and application to the bioequivalence evaluation.
Method Determination of coenzyme Q10 in human plasma by liquid chromatography-tandem mass spectrometry. The plasma sample was extracted twice with n-hexane, then separated on a Capcell Pak C18(35 mm×2.0 mm I.D.,5μm)column using methanol as the mobile phase. A triple quadrupole mass spectrometry equipped with atmospheric pressure chemical ionization (APCI) source was used as the detector and operated in the positive ion mode. Quantitation was performed using multiple reaction monitoring (MRM) of the transitions of m/z 864→m/z 197 and m/z 796→m/z 197 for CoQ10 and the internal standard CoQ9, respectively.
Results The linear concentration range of the calibration curve for coenzyme Q10 was 10.0 ? 1000 ng?mL-1, The lower limit of quantification was 10.0 ng?mL-1. The intra-day and inter-day relative standard deviation over the entire concentration range were less than 8.9%. The accuracy was in the range of -0.9% to 3.8% in terms of relative error. Each sample was chromatographed within 4.5 min.
Conclusion The validated liquid chromatographic?tandem mass spectrometric method was sensitive, specific, rapid and suitable for the bioequivalence evaluation of coenzyme Q10 in humans.
2. Quantitative analysis of hydroxyethyl starch in human plasma and urine and their applications
Background Hydroxyethyl starch is a mixture of glucose polymers of varying chain length and various substitution with hydroxyethyl groups. It is necessary to hydrolyze hydroxyethly starch (HES) into glucose or hydroxyethyl glucose monomers when analysis its concentration in samples. Glucose is an endogenous substance. It is fundamental to develop a sensitive and specific method to eliminate the interference of endogenous glucose and quantify the concenteation of glucose monomers after hydrolysis in human plasma and urine samples.
Objective To develop and validate a specific, sensitive and rapid analytical method for indirect determination of hydroxyethly starch in human plasma and application to the clinical pharmacokinetic study.
Method Indirect determination of hydroxyethly starch in human plasma and urine by hexokinase method. Plasma and urine samples were deproteinated by trichloroacetic acid followed by centrifugation. Supernatant centrifugate was precipitated by acetone, then acidly hydrolyzed with 4M trifluoroaceticacid (1.5 h, 100°C.) to produce monomers. Glucose determination performed using an enzymatic test kit based on hexokinase/glucose-6-phosphatese and hydroxyethly starch concentration was calculated according to the determined concentration.
Results The linear concentration range of the calibration curve was 0.25-10.0 mg?mL-1 and the lower limit of quantification was 0.25 mg?mL-1. The intra-day and inter-day relative standard deviation of plasma samples’determination over the entire concentration range were less than 13.2%. The accuracy was in the range of -2.0% to -0.7% in terms of relative error. The intra-day relative standard deviation of urine samples’determination was less than 4.8%. The accuracy was in the range of -3.9% to -1.2%. The mean analysis time was just 8 min for 50 processed samples.
Conclusion The validated hexokinase analytical method was sensitive, rapid and suitable for the clinical pharmacokinetic study of hydroxyethly starch in humans.
背景辅酶Q10是人体能自身合成的脂类物质,是线粒体呼吸链的辅因子,具有抗氧化作用。它极性较弱,体内本底浓度较高。
目的建立专属、易操作的液相色谱-串联质谱法,测定人血浆中的辅酶Q10,并用于辅酶Q10的生物等效性研究。
方法LC-MS/MS法测定人血浆中的辅酶Q10。血浆样品经正己烷液-液萃取两次,以甲醇为流动相,Capcell Pak C18柱(35 mm×2.0 mm I.D.,5μm)进行分离,采用大气压化学电离源,以多反应监测(MRM)方式进行正离子检测。用于定量分析的离子反应分别为m/z 864→m/z 197(辅酶Q10)和m/z 796→m/z 197(内标辅酶Q9)。
结果测定血浆中辅酶Q10的线性范围为10.0 ~ 1000 ng?mL-1,定量下限可达10.0 ng?mL-1,日内、日间精密度(RSD)均小于8.9%,准确度(RE)在-0.9% ~ 3.8%之间。单个样品分析时间为4.5 min。
结论本文所建立的液相色谱-串联质谱法灵敏,专属,快速,适用于辅酶Q10的血药浓度测定及其生物等效性评价。
2.血浆和尿中羟乙基淀粉定量分析方法研究和应用
背景羟乙基淀粉是由不同链长度和不同羟乙基取代位点的葡萄糖多聚体组成。它作为代血浆,临床上主要用于补充血容量不足。在羟乙基淀粉浓度测定时,需要将其水解为单体,通过测定葡萄糖单体浓度,从而计算羟乙基淀粉浓度。因此,在其浓度测定时,需排除内源性本底浓度的干扰,建立灵敏、专属的分析方法。
目的建立灵敏、专属的定量分析方法,测定人血浆和尿中的羟乙基淀粉,并用于羟乙基淀粉200/0.5的人体药代动力学研究。
方法己糖激酶法间接测定人血浆和尿样中的羟乙基淀粉。血浆和尿样先用三氯乙酸沉淀去除血浆蛋白,再用丙酮沉淀上清液中的羟乙基淀粉,最后,用三氟乙酸(油浴1.5 h,100°C)水解,采用己糖激酶法进行测定,从而计算人血浆和尿样中的羟乙基淀粉。
结果测定血浆和尿中羟乙基淀粉的线性范围均为0.250 ~ 10.0 mg?mL-1,定量下限均为0.25 mg?mL-1;测定血浆中羟乙基淀粉的日内、日间精密度(RSD)均小于13.2%,准确度(RE)在-2.0% ~ -0.7%之间;测定尿中羟乙基淀粉的日内精密度小于4.8%,准确度(RE)在-3.9% ~ -1.2%之间。平均8 min能测定50个经预处理后的样品。
结论本文所建立的己糖激酶法灵敏,快速,已成功用于羟乙基淀粉200/0.5注射液的临床药代动力学研究。
1. Quantitative analysis of coenzyme Q10 in human plasma and its applications
Background Coenzyme Q10 (CoQ10) is an endogenous enzyme cofactor that exsits in all living cells in humans. It is an electron carrier in the mitochondrial respiratory chain and act as a lipid-soluble antioxidant.
Objective To develop and validate a specific and rapid liquid chromatographic?tandem mass spectrometric method for determination of coenzyme Q10 in human plasma and application to the bioequivalence evaluation.
Method Determination of coenzyme Q10 in human plasma by liquid chromatography-tandem mass spectrometry. The plasma sample was extracted twice with n-hexane, then separated on a Capcell Pak C18(35 mm×2.0 mm I.D.,5μm)column using methanol as the mobile phase. A triple quadrupole mass spectrometry equipped with atmospheric pressure chemical ionization (APCI) source was used as the detector and operated in the positive ion mode. Quantitation was performed using multiple reaction monitoring (MRM) of the transitions of m/z 864→m/z 197 and m/z 796→m/z 197 for CoQ10 and the internal standard CoQ9, respectively.
Results The linear concentration range of the calibration curve for coenzyme Q10 was 10.0 ? 1000 ng?mL-1, The lower limit of quantification was 10.0 ng?mL-1. The intra-day and inter-day relative standard deviation over the entire concentration range were less than 8.9%. The accuracy was in the range of -0.9% to 3.8% in terms of relative error. Each sample was chromatographed within 4.5 min.
Conclusion The validated liquid chromatographic?tandem mass spectrometric method was sensitive, specific, rapid and suitable for the bioequivalence evaluation of coenzyme Q10 in humans.
2. Quantitative analysis of hydroxyethyl starch in human plasma and urine and their applications
Background Hydroxyethyl starch is a mixture of glucose polymers of varying chain length and various substitution with hydroxyethyl groups. It is necessary to hydrolyze hydroxyethly starch (HES) into glucose or hydroxyethyl glucose monomers when analysis its concentration in samples. Glucose is an endogenous substance. It is fundamental to develop a sensitive and specific method to eliminate the interference of endogenous glucose and quantify the concenteation of glucose monomers after hydrolysis in human plasma and urine samples.
Objective To develop and validate a specific, sensitive and rapid analytical method for indirect determination of hydroxyethly starch in human plasma and application to the clinical pharmacokinetic study.
Method Indirect determination of hydroxyethly starch in human plasma and urine by hexokinase method. Plasma and urine samples were deproteinated by trichloroacetic acid followed by centrifugation. Supernatant centrifugate was precipitated by acetone, then acidly hydrolyzed with 4M trifluoroaceticacid (1.5 h, 100°C.) to produce monomers. Glucose determination performed using an enzymatic test kit based on hexokinase/glucose-6-phosphatese and hydroxyethly starch concentration was calculated according to the determined concentration.
Results The linear concentration range of the calibration curve was 0.25-10.0 mg?mL-1 and the lower limit of quantification was 0.25 mg?mL-1. The intra-day and inter-day relative standard deviation of plasma samples’determination over the entire concentration range were less than 13.2%. The accuracy was in the range of -2.0% to -0.7% in terms of relative error. The intra-day relative standard deviation of urine samples’determination was less than 4.8%. The accuracy was in the range of -3.9% to -1.2%. The mean analysis time was just 8 min for 50 processed samples.
Conclusion The validated hexokinase analytical method was sensitive, rapid and suitable for the clinical pharmacokinetic study of hydroxyethly starch in humans.
引文
[1] Crane FL, Hatefi Y., Lester RI, et al. Isolation of a quinone from beef heart mitochondria[J]. Biochimica et Biophys. Acta, 1957, 25: 220-221
[2] Morton RA, Wilson GM, Lowe JS, et al. Ubiquinone[J]. Chemical Industry, 1957: 1649
[3] Folkers K, Wolf DE, Hoffman CH, et al. Coenzyme Q structure studies on the coenzyme Q group[J]. J Am Chem Soc, 1958, 80: 4752.
[4] Mitchell P. Possible molecular mechanisms of the protonmotive function of cytochrome systems[J]. J Theoret Biol, 1976, 62: 327-367
[5] Elmberger PG, Kalen A, Brunk UT, et al. Discharge of newly-synthesized dolichol and ubiquinone with lipoproteins to rat liver perfusate and to the bile]J]. Lipids,1989, 24: 919-930
[6] Traber MG, Lne JC, Lagmay NR, Kayden HJ. Studies on the transfer of tocopherol between lipoproteins[J]. Lipids, 1992;27:657-663
[7] Alleva R, Tomasetti M, Bompadre S, et al. Oxidation of LDL and their subfractions: Kinetic aspects and CoQ10 content[J]. Mol Aspects Med, 1997, 18: 105-112
[8] Kalen A, Appelkvist E-L, Dallner G. Age-related changes in the lipid compositions of rat and human tissues[J]. Lipids, 1989, 24: 579-584
[9] Langsjoen PH, Langsjoen AM. The clinical use of HMG CoA-reductase inhibitors and the associated depletion of coenzyme Q10. A review of animal and human publications[J]. Biofactors, 2003, 18: 101-111
[10] Hodgson JM, Watts GF, Playford DA, et al. Coenzyme Q10 improves blood pressure and glycaemic control: a controlled trial in subjects with type 2 diabetes[J]. Eur J Clin Nutr, 2002, 56: 1137-1142
[11] Conklin KA. Coenzyme q10 for prevention of anthracycline-induced[J]. cardiotoxicity, Integr Cancer Ther, 2005, 4: 110-130
[12] Lu WL, Zhang Q, Lee HS, et al. Total coenzyme Q10 concentrations in Asian men following multiple oral 50-mg doses administered as coenzyme Q10 sustained release tablets or regular tablets[J]. Biol Pharm Bull, 2003, 26(1):52-55
[13] Tomono Y, Hasegawa J, Seki T, et al. Pharmacokinetic study of deuterium-labelled coenzyme Q10 in man[J]. Int J Clin Phramacol Ther Toxicol, 1986, 24: 536-541
[14] Weber C, Jakobsen TS, Mortensen SA, et al. Antioxidative effect of dietary coenzyme Q10 in human blood plasma[J]. Int J Vitam Nutr Res, 1994, 64:311-315
[15] Wahlqvist ML, Wattanapenpaiboon N, Savige GS, et al. Bioavailbility of two different formulations of coenzyme Q10 in healthyl subjects[J]. Asia Pacific J Clin Nutr, 1998, 7(1):37-40
[16] Langsjoen PH, Langsjoen AM. Overview of the use of coenzyme Q10 in cardiovascular disease[J]. Biofactors, 1999, 9:273-284
[17] Beal MF, Shults CW. Effects of coenzyme Q10 in Huntington’s disease and early Parkinson’s diseases[J]. BioFactors, 2003, 18:153-161
[18] Treib J, Baron J-F, Grauer MT, et al. An international view of hydroxyethly starches[J]. Intensive Care Med, 1999, 25: 258-268
[19] World Anti-Doping Agency. The 2010 Prohibited list of Substances. 2010, www. wada-ama.org/Documents/World_Anti-Doping_Program/WADP-Prohibited-list/WADA_Pro- hibited_List_2010_EN.pdf, valid from January 1, 2010
[20] Boldt J, Suttner S. Plasma substitutes[J]. Minerva Anestesiol, 2005, 71: 741-758
[21] Treib J, Baron J-F, Grauer MT, et al. An international view of hydroxyethly starches[J]. Intensive Care Med, 1999, 25: 258-268
[22] Junghernrich C, Neff TA. Pharmacokinetics of hydroxyethyl starch[J]. Clin Pharmacokinet, 2005, 44 (7): 681-699
[23] Kozek-Langenecker SA. Effects of hydroxyethyl starch solutions on hemostasis[J]. Anesthesiology, 2005, 103: 654-660
[24] De Jonge E, Levi M. Effects of different plasma substitutes on blood coagulation: a comparative review[J]. Crit Care Med, 2001, 29(6): 1261-1267
[25] Duncan AJ, Mills K, Eaton S, et al. Determination of coenzyme Q10 status in blood mononuclear cells, skeletal muscle, and plasma by HPLC with di-propoxy-coenzyme Q10 as an internal standard[J]. Clinical Chemistry, 2005,51(12): 2380-2382
[26] Kommuru TR, Khan MA, Ashraf M, et al. A simplified chromatographic method for quantitative determination of coenzyme Q10 in dog plasma[J]. J Pharm Biomed Anal, 1998, 16:1037-1040
[27]张伟英,李士敏,王彤文等.辅酶Q10片药动学与人体相对生物利用度试验[J].中国医院药学杂志, 2004, 24 (9): 527-529
[28] Mosca F, Fattorini D, Bompardre S, et al. Assay of coenzyme Q10 in plasma by a single dilution step[J]. Anal Biochem, 2002, 305:49-54
[29] Tang HP, Miles VM, DeGrauw A, et al. HPLC analysis of reduced and oxidized coenzyme Q10 in human plasma[J]. Clin Chem, 2001, 47:256-265
[30] Yamashita S, Yamamoto Y. Simultaneous detection of ubiquinol and ubiquinone in human plasma as a marker of oxidative stress[J]. Anal Biochem, 1997, 250:66-73
[31] Wang Q, Lee BL, Ong CN. Automated high-performance liquid chromatographic method with pre-column reduction for the determination of ubiquinol and ubiquinone plasma[J]. J Chromatogr B, 1999, 726: 297-302
[32] Li L, Pabbisetty D, Carvalho P, et al. Analysis of CoQ10 in rat serum by ultra-performance liquid chromatography mass pectrometry after oral administration[J]. J Pharm Biomed Anal, 2008, 46:137-142
[33] Hansen G, Christensen P, Lund T, et al. Sensitive and selective analysis of coenzyme Q10 in human serum by negative APCI LC-MS[J]. Analyst, 2004, 129:45-50
[34] Teshima K, Kondo T. Analytical method for ubiquione-9 and ubiquinone-10 in rat tissues by liquid chromatography/turbo ion spray tandem mass sprctrometry with 1-alkylamine as an additive to the mobile phase[J]. Anal Biochem, 2005, 338:12-19
[35] Jimenez J, Priego-Capote F, Mata-Granados JM, et al. Determination of the ubiquinol-10 and ubiquinone-10 (coenzyme Q10) in human serum by liquid chromatography tandem mass spectrometry to evaluate the oxidative stress[J]. J Chromatogr A, 2007, 1175:242-248
[36] Finckh B, Kontush A, Commentz J, et al. Monitoring of ubiquinol-10, ubiquinone-10, carotenoids, and tocopherols in neonatal plasma microsamples using high-performance liquid chromatography with coulometric electrochemical detection[J]. Anal Biochem, 1995, 232:210-216
[37] Lu. J, Measurement of coenzyme Q10 in clinical practice[J]. Clin Chim Acta, 2007, 384:180-181
[38] Shah VP, Midha KK, Findlay JW, et al. Bioanalytical method validation– A revisit with a decade of progress[J]. Pharm Res, 2000, 17:1551-1557
[39] Miles MV, Horn P, Miles L, et al. Bioequivalence of coenzyme Q10 from over-the-counter supplements[J]. Nutrition Research, 2002, 22: 919-929
[40] Hosoe K, Kitano M, Kishida H, et al. Study on safety and bioavailability of ubiquinol (Kaneka QHTM) after single and 4-week multiple oral administration to healthy volunteers[J]. Regulatory Toxicology and Pharmacology, 2007, 47: 19-28
[41] K?hler H, Zschiedrich H, Linfante A, et al. Clasen R. Die elimination von hydroxy?thylst?rke 200/0,5, dextran 40 und oxypolygelatine[J]. Klin Wochenschr, 1982, 60: 293-301
[42] Wilkes NJ, Woolf RL, Powanda MC, et al. Hydroxyethyl starch in balanced electrolyte solution (Hextend?)—pharmacokinetic and pharmacodynamic profiles in healthy volunteers[J]. Anesth Analg, 2002, 94: 538-544
[43]曾援,吴新民,杜敏逸,等. 6%羟乙基淀粉200/0.5的药代动力学研究[J].临床麻醉性杂志,2008,24 (3): 189-191
[44] Thyes C, Madjdpour C, Frascarolo P, et al. Effect of high- and low-molecular-weight low-substituted hydroxyethyl starch on blood coagulation during acute normovolemic hemodilution in pigs[J]. Anesthesiology, 2006, 105: 1228-1237
[45] Rehm M, Haller M, Orth V, et al. Changes in blood volume and hematocrit during acutepreoperative volume loading with 5% albumin or 6% hetastarch solutions in patients before radical hysterectomy[J]. Anesthesiology, 2001, 95: 849-856
[46] Waitzinger J, Bepperling F, Pabst G, et al. Hydroxyethyl starch (HES) [130/0.4], a new HES specification:pharmacokinetics and safety after multiple infusions of 10% solution in healthy volunteers[J]. Drugs R&D, 2003, 4 (3): 149-157
[47] Jungheinrich C, Scharpf R, Wargenau M, et al. The pharmacokinetics and tolerability of an intravenous infusion of the new hydroxyethyl starch 130/0.4 (6%, 500 mL) in mild-to-severe renal impairment[J]. Anesth Analg, 2002, 95: 544-51
[48] Lenz L, Schimetta W, Polz W, et al. Intestinal elimination of hydroxyethly starch[J]? Intensive Care Med, 2000,26:733-739
[49] Lehmann GB, Asskail F, Boll M, et al. HES 130/0.42 shows less alteration of pharmacokinetics than HES 200/0.5 when dosed repeatedly[J]. British Journal of Anaesthesia, 2007, 98 (5): 635-644.
[50] Thevis M, Opfermann G, Schanzer W. Detection of the plasma volume expander hydroxyethyl starch in human urine[J]. J Chromatogr B, 2000, 744: 345-350
[51] Deventer K, Van Eenoo P, Delbeke FT. Detection of hydroxyethyl starch (HES) in human urine by liquid chromatography-mass spectrometry[J]. J Chromatogr B, 2006, 834: 217-220
[52] Guddat S, Thevis M, Thomas A, et al. Rapid screening of polysaccharide-based plasma volume expanders dextran and hydroxyethyl starch in human urine by liquid chromatography–tandem mass spectrometry[J]. Biomed Chromatogr, 2008, 22: 695-701
[53] Gallego RG, Segura J. Rapid screening of plasma volume expanders in urine using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry[J]. Rapid Commun. Mass spectrum, 2004, 18: 1324-1330
[54] Sommermeyer K, Cech F, Schossow R. Differences in chemical structures between waxy maize- and potato starch-based hydroxyethyl starch volume therapeutics[J]. Transfusion Alternatives in Transfusion Medicine, 2007, 9: 127-133
[55] Lyon ME, Baskin LB, Braakman S, et al. Interference studies with two hospital-grade and two home-grade glucose meters[J]. Diabetes Technology & Therapeutics, 2009, 11(10): 641-647
[56]周丽萍,姜旭淦,徐军.葡萄糖脱氢酶法测定血清葡萄糖的方法学评价[J].江苏大学学报, 2006, 16(4): 301-303
[57] Weidler B, von Bormann B, Sommermeyer K, et al. Pharmakokinetische merkmale als kriterien fur den klinischen einsatz von hydroxyethylstarke[J]. Arzneimittelforschung, 1991, 41: 494-498
[58] Mishler JM. Pharmakokinetik mittelmolekularer hydroxy?thylst?rke (HAS200/0,5) [J]. Infusionsther, 1980, 7: 96-102
[2] Morton RA, Wilson GM, Lowe JS, et al. Ubiquinone[J]. Chemical Industry, 1957: 1649
[3] Folkers K, Wolf DE, Hoffman CH, et al. Coenzyme Q structure studies on the coenzyme Q group[J]. J Am Chem Soc, 1958, 80: 4752.
[4] Mitchell P. Possible molecular mechanisms of the protonmotive function of cytochrome systems[J]. J Theoret Biol, 1976, 62: 327-367
[5] Elmberger PG, Kalen A, Brunk UT, et al. Discharge of newly-synthesized dolichol and ubiquinone with lipoproteins to rat liver perfusate and to the bile]J]. Lipids,1989, 24: 919-930
[6] Traber MG, Lne JC, Lagmay NR, Kayden HJ. Studies on the transfer of tocopherol between lipoproteins[J]. Lipids, 1992;27:657-663
[7] Alleva R, Tomasetti M, Bompadre S, et al. Oxidation of LDL and their subfractions: Kinetic aspects and CoQ10 content[J]. Mol Aspects Med, 1997, 18: 105-112
[8] Kalen A, Appelkvist E-L, Dallner G. Age-related changes in the lipid compositions of rat and human tissues[J]. Lipids, 1989, 24: 579-584
[9] Langsjoen PH, Langsjoen AM. The clinical use of HMG CoA-reductase inhibitors and the associated depletion of coenzyme Q10. A review of animal and human publications[J]. Biofactors, 2003, 18: 101-111
[10] Hodgson JM, Watts GF, Playford DA, et al. Coenzyme Q10 improves blood pressure and glycaemic control: a controlled trial in subjects with type 2 diabetes[J]. Eur J Clin Nutr, 2002, 56: 1137-1142
[11] Conklin KA. Coenzyme q10 for prevention of anthracycline-induced[J]. cardiotoxicity, Integr Cancer Ther, 2005, 4: 110-130
[12] Lu WL, Zhang Q, Lee HS, et al. Total coenzyme Q10 concentrations in Asian men following multiple oral 50-mg doses administered as coenzyme Q10 sustained release tablets or regular tablets[J]. Biol Pharm Bull, 2003, 26(1):52-55
[13] Tomono Y, Hasegawa J, Seki T, et al. Pharmacokinetic study of deuterium-labelled coenzyme Q10 in man[J]. Int J Clin Phramacol Ther Toxicol, 1986, 24: 536-541
[14] Weber C, Jakobsen TS, Mortensen SA, et al. Antioxidative effect of dietary coenzyme Q10 in human blood plasma[J]. Int J Vitam Nutr Res, 1994, 64:311-315
[15] Wahlqvist ML, Wattanapenpaiboon N, Savige GS, et al. Bioavailbility of two different formulations of coenzyme Q10 in healthyl subjects[J]. Asia Pacific J Clin Nutr, 1998, 7(1):37-40
[16] Langsjoen PH, Langsjoen AM. Overview of the use of coenzyme Q10 in cardiovascular disease[J]. Biofactors, 1999, 9:273-284
[17] Beal MF, Shults CW. Effects of coenzyme Q10 in Huntington’s disease and early Parkinson’s diseases[J]. BioFactors, 2003, 18:153-161
[18] Treib J, Baron J-F, Grauer MT, et al. An international view of hydroxyethly starches[J]. Intensive Care Med, 1999, 25: 258-268
[19] World Anti-Doping Agency. The 2010 Prohibited list of Substances. 2010, www. wada-ama.org/Documents/World_Anti-Doping_Program/WADP-Prohibited-list/WADA_Pro- hibited_List_2010_EN.pdf, valid from January 1, 2010
[20] Boldt J, Suttner S. Plasma substitutes[J]. Minerva Anestesiol, 2005, 71: 741-758
[21] Treib J, Baron J-F, Grauer MT, et al. An international view of hydroxyethly starches[J]. Intensive Care Med, 1999, 25: 258-268
[22] Junghernrich C, Neff TA. Pharmacokinetics of hydroxyethyl starch[J]. Clin Pharmacokinet, 2005, 44 (7): 681-699
[23] Kozek-Langenecker SA. Effects of hydroxyethyl starch solutions on hemostasis[J]. Anesthesiology, 2005, 103: 654-660
[24] De Jonge E, Levi M. Effects of different plasma substitutes on blood coagulation: a comparative review[J]. Crit Care Med, 2001, 29(6): 1261-1267
[25] Duncan AJ, Mills K, Eaton S, et al. Determination of coenzyme Q10 status in blood mononuclear cells, skeletal muscle, and plasma by HPLC with di-propoxy-coenzyme Q10 as an internal standard[J]. Clinical Chemistry, 2005,51(12): 2380-2382
[26] Kommuru TR, Khan MA, Ashraf M, et al. A simplified chromatographic method for quantitative determination of coenzyme Q10 in dog plasma[J]. J Pharm Biomed Anal, 1998, 16:1037-1040
[27]张伟英,李士敏,王彤文等.辅酶Q10片药动学与人体相对生物利用度试验[J].中国医院药学杂志, 2004, 24 (9): 527-529
[28] Mosca F, Fattorini D, Bompardre S, et al. Assay of coenzyme Q10 in plasma by a single dilution step[J]. Anal Biochem, 2002, 305:49-54
[29] Tang HP, Miles VM, DeGrauw A, et al. HPLC analysis of reduced and oxidized coenzyme Q10 in human plasma[J]. Clin Chem, 2001, 47:256-265
[30] Yamashita S, Yamamoto Y. Simultaneous detection of ubiquinol and ubiquinone in human plasma as a marker of oxidative stress[J]. Anal Biochem, 1997, 250:66-73
[31] Wang Q, Lee BL, Ong CN. Automated high-performance liquid chromatographic method with pre-column reduction for the determination of ubiquinol and ubiquinone plasma[J]. J Chromatogr B, 1999, 726: 297-302
[32] Li L, Pabbisetty D, Carvalho P, et al. Analysis of CoQ10 in rat serum by ultra-performance liquid chromatography mass pectrometry after oral administration[J]. J Pharm Biomed Anal, 2008, 46:137-142
[33] Hansen G, Christensen P, Lund T, et al. Sensitive and selective analysis of coenzyme Q10 in human serum by negative APCI LC-MS[J]. Analyst, 2004, 129:45-50
[34] Teshima K, Kondo T. Analytical method for ubiquione-9 and ubiquinone-10 in rat tissues by liquid chromatography/turbo ion spray tandem mass sprctrometry with 1-alkylamine as an additive to the mobile phase[J]. Anal Biochem, 2005, 338:12-19
[35] Jimenez J, Priego-Capote F, Mata-Granados JM, et al. Determination of the ubiquinol-10 and ubiquinone-10 (coenzyme Q10) in human serum by liquid chromatography tandem mass spectrometry to evaluate the oxidative stress[J]. J Chromatogr A, 2007, 1175:242-248
[36] Finckh B, Kontush A, Commentz J, et al. Monitoring of ubiquinol-10, ubiquinone-10, carotenoids, and tocopherols in neonatal plasma microsamples using high-performance liquid chromatography with coulometric electrochemical detection[J]. Anal Biochem, 1995, 232:210-216
[37] Lu. J, Measurement of coenzyme Q10 in clinical practice[J]. Clin Chim Acta, 2007, 384:180-181
[38] Shah VP, Midha KK, Findlay JW, et al. Bioanalytical method validation– A revisit with a decade of progress[J]. Pharm Res, 2000, 17:1551-1557
[39] Miles MV, Horn P, Miles L, et al. Bioequivalence of coenzyme Q10 from over-the-counter supplements[J]. Nutrition Research, 2002, 22: 919-929
[40] Hosoe K, Kitano M, Kishida H, et al. Study on safety and bioavailability of ubiquinol (Kaneka QHTM) after single and 4-week multiple oral administration to healthy volunteers[J]. Regulatory Toxicology and Pharmacology, 2007, 47: 19-28
[41] K?hler H, Zschiedrich H, Linfante A, et al. Clasen R. Die elimination von hydroxy?thylst?rke 200/0,5, dextran 40 und oxypolygelatine[J]. Klin Wochenschr, 1982, 60: 293-301
[42] Wilkes NJ, Woolf RL, Powanda MC, et al. Hydroxyethyl starch in balanced electrolyte solution (Hextend?)—pharmacokinetic and pharmacodynamic profiles in healthy volunteers[J]. Anesth Analg, 2002, 94: 538-544
[43]曾援,吴新民,杜敏逸,等. 6%羟乙基淀粉200/0.5的药代动力学研究[J].临床麻醉性杂志,2008,24 (3): 189-191
[44] Thyes C, Madjdpour C, Frascarolo P, et al. Effect of high- and low-molecular-weight low-substituted hydroxyethyl starch on blood coagulation during acute normovolemic hemodilution in pigs[J]. Anesthesiology, 2006, 105: 1228-1237
[45] Rehm M, Haller M, Orth V, et al. Changes in blood volume and hematocrit during acutepreoperative volume loading with 5% albumin or 6% hetastarch solutions in patients before radical hysterectomy[J]. Anesthesiology, 2001, 95: 849-856
[46] Waitzinger J, Bepperling F, Pabst G, et al. Hydroxyethyl starch (HES) [130/0.4], a new HES specification:pharmacokinetics and safety after multiple infusions of 10% solution in healthy volunteers[J]. Drugs R&D, 2003, 4 (3): 149-157
[47] Jungheinrich C, Scharpf R, Wargenau M, et al. The pharmacokinetics and tolerability of an intravenous infusion of the new hydroxyethyl starch 130/0.4 (6%, 500 mL) in mild-to-severe renal impairment[J]. Anesth Analg, 2002, 95: 544-51
[48] Lenz L, Schimetta W, Polz W, et al. Intestinal elimination of hydroxyethly starch[J]? Intensive Care Med, 2000,26:733-739
[49] Lehmann GB, Asskail F, Boll M, et al. HES 130/0.42 shows less alteration of pharmacokinetics than HES 200/0.5 when dosed repeatedly[J]. British Journal of Anaesthesia, 2007, 98 (5): 635-644.
[50] Thevis M, Opfermann G, Schanzer W. Detection of the plasma volume expander hydroxyethyl starch in human urine[J]. J Chromatogr B, 2000, 744: 345-350
[51] Deventer K, Van Eenoo P, Delbeke FT. Detection of hydroxyethyl starch (HES) in human urine by liquid chromatography-mass spectrometry[J]. J Chromatogr B, 2006, 834: 217-220
[52] Guddat S, Thevis M, Thomas A, et al. Rapid screening of polysaccharide-based plasma volume expanders dextran and hydroxyethyl starch in human urine by liquid chromatography–tandem mass spectrometry[J]. Biomed Chromatogr, 2008, 22: 695-701
[53] Gallego RG, Segura J. Rapid screening of plasma volume expanders in urine using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry[J]. Rapid Commun. Mass spectrum, 2004, 18: 1324-1330
[54] Sommermeyer K, Cech F, Schossow R. Differences in chemical structures between waxy maize- and potato starch-based hydroxyethyl starch volume therapeutics[J]. Transfusion Alternatives in Transfusion Medicine, 2007, 9: 127-133
[55] Lyon ME, Baskin LB, Braakman S, et al. Interference studies with two hospital-grade and two home-grade glucose meters[J]. Diabetes Technology & Therapeutics, 2009, 11(10): 641-647
[56]周丽萍,姜旭淦,徐军.葡萄糖脱氢酶法测定血清葡萄糖的方法学评价[J].江苏大学学报, 2006, 16(4): 301-303
[57] Weidler B, von Bormann B, Sommermeyer K, et al. Pharmakokinetische merkmale als kriterien fur den klinischen einsatz von hydroxyethylstarke[J]. Arzneimittelforschung, 1991, 41: 494-498
[58] Mishler JM. Pharmakokinetik mittelmolekularer hydroxy?thylst?rke (HAS200/0,5) [J]. Infusionsther, 1980, 7: 96-102