PH value monitoring during human albumin purification with near infrared spectroscopy and chemometrics

Qiaofeng Sun,Lian Li,Mingyu Wang,Zhongyu Sun,Ronghua Liu,Hengchang Zang,Lei Nie,Jiayue Wang,Fei Wang

doi:10.1142/s1793545818500098

Abstract

Human albumin (HA) is a very important blood product which requires strict quality control strategy. Acid precipitation is a key step which has a great effect on the quality of final product. Therefore, a new method based on quality by design (QbD) was proposed to investigate the feasibility of realizing online quality control with the help of near infrared spectroscopy (NIRS) and chemometrics. The pH value is the critical process parameter (CPP) in acid precipitation process, which is used as the end-point indicator. Six batches, a total of 74 samples of acid precipitation process, were simulated in our lab. Four batches were selected randomly as calibration set and remaining two batches as validation set. Then, the analysis based on material information and three different variable selection methods, including interval partial least squares regression (iPLS), competitive adaptive reweighted sampling (CARS) and correlation coefficient (CC) were compared for eliminating irrelevant variables. Finally, iPLS was used for variables selection. The quantitative model was built up by partial least squares regression (PLSR). The values of determination coefficients ([Formula: see text] and [Formula: see text]), root mean squares error of prediction (RMSEP), root mean squares error of calibration (RMSEC) and root mean squared error of cross validation (RMSECV) were 0.969, 0.953, 0.0496, 0.0695 and 0.0826, respectively. The paired [Formula: see text] test and repeatability test showed that the model had good prediction ability and stability. The results indicated that PLSR model could give accurate measurement of the pH value.

Highlights

As the main plasma protein, Human albumin (HA) plays an important physiological role in human body.[1]
The samples were diluted with deionized water to ethanol content of 10% based on the results by gas chromatography, and the pH value of samples was measured using pH meter at room temperature
Near-infrared quantitative analysis models of pH values during acid precipitation were established, which were used for the determination of pH values and the judgment of the end point of acid precipitation process

Summary

Introduction

As the main plasma protein, Human albumin (HA) plays an important physiological role in human body.[1]. The pH value is used as the process end-point indicator. The pH value greater or less than the pI will produce positive or negative ions, which will lead to increase the solubility of HA and impurity, a®ecting the quality ofnal products. It is important to monitor the trajectory of pH value. Traditional method which is based on the industrial pH meter is not suitable for HA production. The raw material for acid precipitation contains about 40% ethanol,[7] and there is almost no available online industrial pH meters in the market. The measurement of pH values by pH meter is o®-line and time-consuming, so it is unable to meet the needs of online production. A new spectral tool was introduced to investigate the feasibility for pH monitoring during the precipitation process

Objectives

Methods

Results

Conclusion