Development of an LC-MS/MS method for quantitative analysis of Chlorogenic acid in human plasma and its application to a pharmacokinetic study in Chinese patients with advanced solid tumor.

A simple and specific, rapid resolution liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for determination of chlorogenic acid in human plasma using neochlorogenic acid as the internal standard. Plasma samples were precipitated with methanol and separated on a Zorbax C18 column (50 × 2.1 mm, i.d. 1.8 µm) at a flow rate of 0.4 mL/min using a gradient mobile phase of methanol-water containing 0.1% formic acid (v/v). The detection was performed on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring in negative ESI mode. The method was fully validated over the concentration range of 10-2000 ng/mL. The indicators of inter- and intra-day precision (RSD%) were all within 10.7%, and the accuracy (RE%) was ranged from -3.0% to 10.6%. Moreover, we evaluated this bioanalytical method by re-analysis of incurred samples as an additional measure of assay reproducibility. This method was successfully applied to pharmacokinetic study of CGA in Chinese subjects with advanced solid tumor after intramuscular injection administration of Chlorogenic acid for injection (CAFI).

Serum cystatin C assay for the detection of early renal impairment in diabetic patients.

The ability to assess renal function in diabetes patients rapidly and early is of major importance. This study was designed to determine whether cystatin C can replace serum creatinine as the screening marker for reduced glomerular filtration rate (GFR) in type 2 diabetes patients. The study was performed on 51 type 2 diabetic patients. GFR was estimated by the plasma clearance of (99m)Tc-DTPA. The correlation between (99m)Tc-DTPA clearance and levels of serum cystatin C, serum creatinine, and creatinine clearance was determined. Sensitivity and specificity for the diagnosis of renal impairment (defined as GFR<68 ml/min) were calculated by a receiver operating characteristic (ROC) curve for serum cystatin C, serum creatinine, and creatinine clearance. The correlation coefficients with (99m)Tc-DTPA clearance were -0.744 for serum cystatin C, -0.658 for serum creatinine, and +0.625 for creatinine clearance (P<0.001). With a cutoff value of 68 mL/min, the area under the ROC curve (AUC) was 0.891 for cystatin C, 0.77 for creatinine, and 0.753 for creatinine clearance. The AUC was statistically different between serum cystatin C and creatinine clearance (P<0.05). The ROC plot indicates that cystatin C is superior to serum creatinine and creatinine clearance for detecting impaired GFR. Serum cystatin C appropriately reflects GFR in diabetes, and is more efficacious than serum creatinine and creatinine clearance in detecting reduced GFR in type 2 diabetes patients.