New sequential injection analysis (SIA) methods with optical sensing for the determination of N-acetyl-L-cysteine ethyl ester (NACET) have been developed and optimized. NACET is a potential drug and antioxidant with advantageous pharmacokinetics. The methods involve the reduction of Cu(II) in its complexes with neocuproine (NCN), bicinchoninic acid (BCA), and bathocuproine disulfonic acid (BCS) to the corresponding chromophoric Cu(I) complexes by the analyte. The absorbance of the Cu(I) complexes with NCN, BCA, and BCS was measured at their maximum absorbance wavelengths of 458, 562, and 483 nm, respectively. The sensing manifold parameters and experimental conditions were optimized for each of the Cu(II) complexes used. Under optimal conditions, the corresponding linear calibration ranges, limits of detection, and sampling rates were 8.0 × 10⁻⁶–2.0 × 10⁻⁴ mol L⁻¹, 5.5 × 10⁻⁶ mol L⁻¹, and 60 h⁻¹ for NCN; 6.0 × 10⁻⁶–1.0 × 10⁻⁴ mol L⁻¹, 5.2 × 10⁻⁶ mol L⁻¹, and 60 h⁻¹ for BCA; and 4.0 × 10⁻⁶–1.0 × 10⁻⁴ mol L⁻¹, 2.6 × 10⁻⁶ mol L⁻¹, and 78 h⁻¹ for BCS. The Cu(II)-BCS complex was found to be best performing in terms of sensitivity and sampling rate. Usual excipients in pharmaceutical preparations did not interfere with NACET analysis.

A sequential injection analysis method for the determination of glutathione (GSH) in pharmaceuticals has been developed. It is based on the reduction of the Cu(II)-neocuproine complex by GSH and the formation of an orange-yellow colored Cu(I)-neocuproine complex with maximum absorbance at 458 nm. Under optimal conditions the method is characterized by a linear calibration range of 6.0 × 10⁻⁷–8.0 × 10⁻⁵ mol L⁻¹ (A_max = 3270 C_GSH − 0.0010; R² = 0.9983), limit of detection of 2.0 × 10⁻⁷ mol L⁻¹, limit of quantification of 6.7 × 10⁻⁷ mol L⁻¹, repeatability (expressed as relative standard deviation) of 3.8%, and sampling rate of 60 h⁻¹. The newly developed method has been successfully applied to the determination of GSH in pharmaceutical samples with no statistically significant difference between the results obtained and those produced by the standard Pharmacopoeia method.