Evaluation of Cheongmeak DCS TM Reagents for Chemistry Analyzers

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1 임상검사와정도관리 J Lab Med Qual Assur 2010 ; 32: ISSN X Evaluation of Cheongmeak DCS TM Reagents for Chemistry Analyzers Kyeong Seob Shin, Taek Eun Jeong, and Bo Ra Son Department of Laboratory Medicine, Chungbuk National University College of Medicine, Cheongju, Korea 자동화학분석용청맥 DCS TM 생화학시약의평가 신경섭 정택은 손보라 충북대학교의과대학진단검사의학교실 교신저자 : 신경섭우 ) 충북청주시흥덕구개신동산 62 번지, 충북대학교병원진단검사의학과전화 :043) FAX:043) ksshin@chungbuk.ac.kr Background: The evaluation of newly developed reagents for chemical analyzer is essential for an accurate testing of various samples. We evaluated the analytical performance of the DCS TM reagents (Cheongmeak, Korea). Methods: Fifteen chemistry reagents of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyl transferase (GGT), alkaline phosphatase (ALP), total bilirubin, total protein, albumin, blood urea nitrogen (BUN), creatinine, glucose, calcium, inorganic phosphorus, total cholesterol, triglyceride and HDL-cholesterol were tested for precision, linearity and correlation according to CLSI guidelines in the Hitachi 7180 chemistry analyzer (Hitachi High-Technologies Co., Japan). Results: The coefficients of variation (CV) of both within-run and total precision were below 3.98% for all analytes, which fully meets of CLIA 88 decision ranges. Good linearity was shown for all analytes in measurement ranges. Coefficients of correlation were also good for all analytes. Conclusions: DCS TM reagents showed good precision, linearity and correlation. Therefore, the DCS TM reagents could be acceptable for use in routine chemistry analyzers. Key Words:DCS TM reagents, Precision, Linearity, Correlation, Evaluation 서론일반화학검사는입원또는외래환자에게진단및치료과정에서기본적인정보를제공하므로병원에서가장많이시행하고있는검사이다. 현재일반화학검사를위한자동화학검사기기에사용되는검사시약은폐쇄형시스템의시약보다는개방형시스템의다양한시약이이용되고있다. 아직까지외국의수입시약이많이사용되고있지만수년전부터국내여러업체에서일반화학검사시약을제조하여제공하고있으며 [1-4], 이들국내시약의지속적인품질향 상은국내진단시약분야의발전에큰기여를할수있을것이다. 한편다양한일반화학검사시약의올바른선택은검사실의효율성운영및검사실의질적측면에서매우중요하며, 검사실에서는적절한시약의선택을위하여충분한평가를거치는것이필수적이다 [5]. 이에저자들은국산시약인 DCS TM 생화학시약 (Cheongmeak, Daejeon, Korea) 의검사수행능을알아보기위하여일반화학검사항목중 15 항목에대한이들시약의정밀도, 직선성및기존시약과의상관성을평가하였다. 197

2 198 신경섭 정택은 손보라 재료및방법 coefficient of variation) 를구하였다 [6]. 1. 검사장비및평가항목평가에이용된검사장비는 Hitachi 7180 (Hitachi High-Technologies co., Tokyo, Japan) 이었으며매검사일마다 Roche Multical calibrator (Roche Diagnostics, Indianapolis, IN, USA) 로 calibration 을시행한후검사를시행하였다. 평가항목은 alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), total bilirubin, total protein, albumin, glucose, Blood urea nitrogen (BUN), creatinine, calcium, inorganic phosphorus, total cholesterol, triglyceride, HDL-cholesterol 등총 15 종목이었다. 비교기준이되는시약으로는현재본검사실에서사용하고있는 Daichii (Daichii Co., Tokyo, Japan), Roche (Roche Diagnostics, Indianapolis, USA), Wako (Wako Pure Chemical Industries, Ltd., Osaka, Japan), Labmaster (HanLab Co., Korea) 등이었다 (Table 1). 평가기간은 2010 년 1월 15일부터 2010 년 3월 20일까지였다. 2. 정밀도 (precision) 평가 Liquid assayed multiqual level 1 & 3 (Bio-Rad Laboratories Inc., Hercules, CA, USA) 를이용하여 CLSI (Clinical Laboratory Standards Institute) EP5-A 에따라 1 일 2회, 매회 2번씩 20일동안측정하여검사중변이계수 (within-run coefficient of variation) 와총변이계수 (total 3. 직선성 (linearity) 평가상품화된직선성평가물질 (Wako Pure Chemical Industries, Ltd., Osaka, Japan) 및고농도환자검체와식염수를이용하여측정범위를포함하는 5단계 (4:0, 3:1, 2:2, 1:3, 0:4) 의농도로제조한후각검사항목을 4회씩반복측정하여 CLSI EP6-1A 기준에따라직선성을평가하였다 [7]. 4. 기존시약과상관성 (correlation) 평가각검사항목마다 85개의환자검체를선정하여기존에사용하였던일반화학검사시약 (Table 1) 과 DCS TM 생화학시약으로중복검사하여상관성을평가하였다 [8]. 5. 통계정밀도와상관성평가에 Excel statics package (Microsoft corporation, Redmond, WA, USA) 를이용하였다. 정밀도평가에서는평균값, 표준편차와변이계수를구하였고, 상관성평가에서는상관성검증을위하여 Pearson 상관계수를구하고일반선형모델을이용하여회귀분석을같이실시하였다. 결과 1. 정밀도검정모든검사항목의검사중변이계수 (within-run CV) 는 Table 1. Comparison of the principles between DCS reagents and current reagents Analyte Comparative reagent Company Method DCS reagent ALT Roche IFCC (UV without P5P) IFCC (UV without P5P) AST Roche IFCC (UV without P5P) IFCC (UV without P5P) ALP Lab master SSCC (P-NPP, DEA buffer) SSCC (P-NPP, DEA buffer) GGT Wako IFCC IFCC Total bilirubin Wako Oxidation Oxidation Total protein Daiichi Biuret Biuret Albumin Daiichi BCG BCG Glucose Roche Hexokinase, UV Hexokinase, UV BUN Daiichi UV rate (GLDH) UV rate (GLDH) Creatinine Daiichi Jaffe Jaffe Total calcium Daiichi OCPC OCPC Phosphorus Daiichi Fiske Subbarow UV-Molybdate Total Cholesterol Wako Enzymatic, COD-HMMPS Enzymatic, colorimetic Triglyceride Daiichi Enzymatic, colorimetric Enzymatic, colorimetric HDL-cholesterol Daiichi Direct method Direct method Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; ALP, alkaline phosphatase; GG, gamma glutamyl transferase; BUN, blood urea nitrogen; HDL, high density lipoprotein.

3 자동화학분석용청맥 DCS TM 생화학시약의평가 199 Table 2. Within-run and total precision of DCS reagents Analyte (unit) Mean Within-run Total Precision goal (CLIA 88 x 1/4) CV (%) CV (%) Decision level Acceptable (%) ALT (IU/L) U/L AST (IU/L) U/L ALP (IU/L) U/L GGT (IU/L) N/A N/A Total bilirubin mg/dl 10 (mg/dl) mg/dl 5 Total protein (g/dl) g/dl 2.5 Albumin (g/dl) g/dl Glucose (mg/dl) mg/dl BUN (mg/dl) mg/dl Creatinine (mg/dl) mg/dl mg/dl 3.75 Total calcium mg/dl 3.6 (mg/dl) mg/dl 2.3 Phosphorus N/A N/A (mg/dl) Total cholesterol mg/dl 2.5 (mg/dl) Triglyceride mg/dl 6.3 (mg/dl) HDL-cholesterol N/A N/A (mg/dl) Abbreviations: CV, Coefficient variance; N/A, data not available. 3.98% 이하이었고, 총변이계수 (total CV) 는 3.59% 이하로 CLIA 88의허용범위에포함되었다 (Table 2). 2. 직선성평가평가한 15 종목의기울기는 에서 사이였으며상관계수 (r) 는 이상이었다 (Table 3).

4 200 신경섭 정택은 손보라 Table 3. The linearity of DCS reagents Analyte (unit) Concentration range Regression equation Correlation coefficient (r) ALT (IU/L) 0-1,508 Y=1.0024x AST (IU/L) 0-1,525 Y=1.0005x ALP (IU/L) 0-2,915 Y=1.0005x GGT (IU/L) 0-1,988 Y=1.0004x Total bilirubin (mg/dl) Y=1.0001x Total protein (mg/dl) Y=1.0067x Albumin (g/dl) Y=0.9999x Glucose (mg/dl) Y=0.9966x BUN (mg/dl) Y=1.0021x Creatinine (mg/dl) Y=1.0024x Total calcium (mg/dl) Y=1.0031x Phosphorus (mg/dl) Y=1.0038x Total Cholesterol (mg/dl) Y=1.0010x Triglyceride (mg/dl) Y=0.9997x HDL-cholesterol Y=0.9965x Table 4. The result of comparison of DCS reagent with other reagents Analyte (unit) Correlation coefficient (r) Slope Y-intercept ALT (IU/L) AST (IU/L) ALP (IU/L) GGT (IU/L) Total bilirubin (mg/dl) Total protein (mg/dl) Albumin (g/dl) Glucose (mg/dl) BUN (mg/dl) Creatinine (mg/dl) Total calcium (mg/dl) IP (mg/dl) Total Cholesterol (mg/dl) Triglyceride (mg/dl) HDL-cholesterol

5 자동화학분석용청맥 DCS TM 생화학시약의평가 기존시약과상관성평가상관성평가를시행한 15 항목모두에서상관계수가 이상으로측정되어 (Table 4, Fig. 1)), 기존시약과우수한상관성을보였다. Fig. 1. The graphic results of comparison between DCS reagents and current reagents.

6 202 신경섭 정택은 손보라 Fig. 1. The graphic results of comparison between DCS reagents and current reagents (continued).

7 자동화학분석용청맥 DCS TM 생화학시약의평가 203 Fig. 1. The graphic results of comparison between DCS reagents and current reagents (continued). 고찰최근국내에서일반화학검사용시약의제조및공급이늘어남에따라이에대한시약의평가도자주보고되고있다 [1-4]. 본연구는현재충북대학교병원에서사용되고있는같은원리의제품과국산시약인 DCS TM 생화학시약에대하여상관성을평가하였고이시약의정밀도와직선성에대한연구를시행하였다. 정밀도평가에서 CLIA 88에서제시하는임상적결정농도와유사한농도의 2가지정도관리물질을이용하여정밀도를평가하였는데, CLIA 88에제시되어있는항목은모두 CLIA 88의기준을만족시켰다 [5]. GGT, Phosphorus 은 CLIA 88에서정밀도의목표치가규정되지않았지만총 CV 가각각 2.38% 와 2.51% 로 Fraser[9] 의 biological variation 개념에근거한허용정밀도 6.9% 와 4.3% 이내였다. HDLcholesterol의총 CV도 1.04% 로우수한정밀도를나타내었 다 (Table 2). 상품화된고농도의직선성평가시료와고농도의환자검체를이용하여생리식염수로희석하여직선성평가를시행하였다. 임상검체에서측정되는농도보다충분히높은범위에서모든항목의회귀방정식은직선으로나타났고, 결정계수 (r) 도 이상으로우수하였다 (Table 3). 상관성평가는저농도와고농도를포함하여환자검체 85 개를사용하여충북대학교병원에서기존에사용하고있는동일검사방법의시약과비교하였다. 기존시약과비교한 15 개검사종목의상관관계 (r) 는모든항목이 (calcium 및 HDL-cholesterol 의상관계수 ) 이상으로우수하였다 (Fig. 1). Calcium, phosphorus, total protein 그리고 albumin 등의항목은정상보다농도가높거나낮은검체가많지않았으나상관성은각각 0.992, 0.995, 그리고 0.996이었으며고농도를포함한직선성도우수하였다. 이상의결과를종합하여볼때, 새로개발된 DCS TM 생화

8 204 신경섭 정택은 손보라 학시약은기존의시약과비교하여정밀도, 직선성및상관성이우수하여다양한임상화학검사장비에적용이가능하다고사료된다. 추후에임상상황에서흔히나타날수있는용혈, 고지혈증및황달등의간섭물질에대한평가등이더필요할것이다. 요약배경 : 새롭게개발된생화학검사시약의사전평가는정확한검사를위해필수적이다. 저자들은 DCS TM 생화학시약 (Cheongmeak, Korea) 의검사수행능을평가하였다. 방법 : ALT, AST, GGT, ALP, total bilirubin, total protein, albumin, BUN, creatinine, glucose, calcium, inorganic phosphorus, total cholesterol, triglyceride, HDL-cholesterol 등총 15 종목에대한시약의정밀도, 직선성및시약의상관성을 Hitachi 7180 (Hitachi High- Technologies Co., Japan) 를이용하여 CLSI 지침에따라평가하였다. 결과 : 정밀도는평가한모든종목에서검사중정밀도변이계수와총변이계수가 3.98% 이하로 CLIA 88의결정범위에속하였다. 다양한측정범위에서모든항목의직선성은우수하였고, 기존시약과의상관성도우수하였다. 결론 : DCS TM 생화학시약은우수한정밀도, 직선성및기존시약과상관성을보여임상검사실에서생화학검사시약으로도입하는데무리가없을것으로사료된다. 참고문헌 1. Cho H-J, Ki C-S, Lee KO, Ok Y-J, Kim SM, Lee S-Y, et al. Evaluation for the precision, linearity and comparision of In Wha Liqchem reagent for the chemistry autoanalyzer. J Clin Pathol Qual Control 2001;23: ( 조현정, 기창석, 이기오, 옥윤주, 김소미, 이수연등. 자동화학검사용인화 Liqchem 액상시약의정밀도, 직선성및상관성평가. 임상병리와정도관리 2001;22: ) 2. Lee W, Kim Y, Chun S, Min WK. Evaluation of LabMaster reagents for chemistry autoanalyzer. J Lab Med Qual Assur 2004;26: ( 이우창, 김윤희, 전사일, 민원기. 자동화학검사용한랩랩마스타시약의평가. 임상검사와정도관리 2004;26: ) 3. Woo H-Y, Kim YJ, Park H. Evaluation of HiSense TM reagents for chemistry autoanalyzer. J Lab Med Qual Assur 2006;28: ( 우희연, 김영재, 박효순. 자동화학검사용 HiSense TM 시약의평가. 임상검사와정도관리 2006;28: ) 4. Kim YS, Lee HK, Kim S-Y, Seo EJ, Min KO, Kwon HJ. Evaluation of BD Lab reagents for chemistry analyzers. J Lab Med Qual Assur 2007;29: ( 김영식, 이혜경, 김수영, 서은주, 민기옥, 권희정. 일반화학분석기용 BD Lab 시약에대한평가. 임상검사와정도관리 2007;29: ) 5. Linnet K and Boyd JC. Selection and analytical evaluation of methods with statistical techniques. In: Burtis CA and Ashwood ER, eds. Tietz textbook of clinical chemistry and molecular diagnostics. 4th ed. Philadelphia: Elsevier Saunders, 2006: Clinical Laboratory Standards Institute, ed. Evaluation of precision performance of clinical chemistry devices: approved guideline. CLSI document EP5-A. Wayne: Clinical Laboratory Standards Institute, Clinical Laboratory Standards Institute, ed. Evaluation of the Linearity of quantitative measurement procedures: a statistical approach; approved guideline. CLSI document EP6-A. Wayne: Clinical Laboratory Standards Institute, Clinical Laboratory Standards Institute, ed. Method comparison and bias estimation using patient samples: approved guideline. 2nd ed. CLSI document EP9-A2. Wayne: Clinical Laboratory Standards Institute, Fraser CG, ed. Biological variation: from principles to practice. Washington, DC: AACC Press, 2001:50-4