Matsuzawa T, Hayashi Y, Nomura M, Unno T, Igarashi T, Furuya T, Sekita K, Ono A, Kurokawa Y, Hayashi Y
Clinical Pathology Working Group, Japan Pharmaceutical Manufacturers Association, Tokyo, Japan.
J Toxicol Sci. 1997 Feb;22(1):25-44. doi: 10.2131/jts.22.25.
A control survey was conducted to check the accuracy of automated analyzers used in the evaluation of clinical chemistry parameters in nonclinical toxicology studies. Pooled serum samples from male Sprague-Dawley rats were delivered refrigerated to each facility 98 laboratory facilities throughout Japan within 18 hours after sample preparation and analyzed. Commercially available normal human serum samples from a single lot were also analyzed at the same time. Survey results were divided into three categories. (1) Parameters with small coefficient of variation (CV) values for both rat and human serum samples included protein, glucose, cholesterol (CHO), urea nitrogen (UN), sodium (Na), potassium (K), chloride (Cl), calcium (Ca), and inorganic phosphate (IP). Definition of normal values in rats should be straight forward for these parameters. (2) Parameters with large CV values, but with a relatively good correlation between rat and human values include triglycerides (TG), glutamic oxaloacetic transaminase/aspartate aminotransferase (GOT/AST), glutamic pyruvic transaminase/alanine aminotransferase (GPT/ALT), and alkaline phosphatase (ALP). Measurements based on different principles gave different mean values, and this values contributed to the increase in CV values. Assessment of normal values would require a consideration of the measurement principles. (3) Parameters with large CV values only in rat serum samples included albumin (albumin/globulin ratio: A/G ratio), creatinine (CRE), and total bilirubin(BIL). Reactivity was different in rat albumin (ALB), depending on the reagents used. This difference needs to be corrected with values available by electrophoresis, or adjusted by rat ALB values, because of the lack of an appropriate measurement method. The enzyme method gave low values for rat CRE, which suggests the need for further examination of this method. The BIL values were extremely low in rat samples. It seems to be necessary to select appropriate methods to measure clinical pathology parameters correctly for rats. There was no deviation in values due solely to the mechanical operations of the analytical equipment. Non-standard initial settings of the equipment (equipment originally intended for human samples, but now applied to animal samples) was the main cause of the wide range of analytical values seen.
进行了一项对照调查，以检查用于非临床毒理学研究中临床化学参数评估的自动分析仪的准确性。将雄性Sprague-Dawley大鼠的混合血清样本在制备后18小时内冷藏运送到日本各地的98个实验室设施，并进行分析。同时还对来自同一批次的市售正常人血清样本进行了分析。调查结果分为三类。（1）大鼠和人血清样本变异系数（CV）值较小的参数包括蛋白质、葡萄糖、胆固醇（CHO）、尿素氮（UN）、钠（Na）、钾（K）、氯（Cl）、钙（Ca）和无机磷（IP）。对于这些参数，大鼠正常值的定义应该很简单。（2）CV值较大，但大鼠和人值之间相关性相对较好的参数包括甘油三酯（TG）、谷草转氨酶/天冬氨酸转氨酶（GOT/AST）、谷丙转氨酶/丙氨酸转氨酶（GPT/ALT）和碱性磷酸酶（ALP）。基于不同原理的测量给出了不同的平均值，这些值导致CV值增加。正常值的评估需要考虑测量原理。（3）仅在大鼠血清样本中CV值较大的参数包括白蛋白（白蛋白/球蛋白比率：A/G比率）、肌酐（CRE）和总胆红素（BIL）。大鼠白蛋白（ALB）的反应性因所用试剂而异。由于缺乏合适的测量方法，这种差异需要用电泳可得的值进行校正，或用大鼠ALB值进行调整。酶法测得的大鼠CRE值较低，这表明需要对该方法进行进一步检查。大鼠样本中的BIL值极低。似乎有必要选择合适的方法来正确测量大鼠的临床病理参数。分析值的差异并非仅由分析设备的机械操作导致。设备的非标准初始设置（原本用于人类样本但现在应用于动物样本的设备）是观察到分析值范围广泛的主要原因。
