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A simple, rapid and sensitive liquid chromatography with tandem mass spectrometry method for the determination of periplocymarin in human blood and urine was developed. The digoxin-d3 was used as an internal standard. Periplocymarin and digoxin-d3 (IS) were processed with ethyl acetate by liquid-liquid extraction. The chromatographic separation was performed on a Shim-pack XR-ODSIII C18 column with a 7 min gradient elution using methanol-ammonium formate (5 mmol/L) as mobile phase at a flow rate of 0.3 mL/min (65:35, v/v). The detection was performed on a triple quadrupole tandem mass spectrometer using positive-ion mode electrospray ionization in selected reaction monitoring mode. The periplocymarin was well separated from the internal standard. Two calibration curves were linear within the concentration range 0.01-1 μg/mL. The limit of detection and quantification of blood and urine samples were both estimated at 0.005 and 0.01 μg/mL. The interday and intraday precisions, accuracy, and recovery were assessed to verify this method. The results showed that the method was suitable for the determination of periplocymarin in forensic toxicological analysis and clinical diagnosis.

Aims: Diabetic kidney disease (DKD) is a severe microvascular complication frequently associated with type 1 and type 2 diabetes mellitus. The objective of this work was to evaluate the relevance of PI3K/Akt pathway polymorphisms and DKD susceptibility by a meta‐analysis. Methods: Case–control studies related to the relationship between PI3K/Akt pathway polymorphisms and DKD risk were searched from Pubmed, Embase, Cochrane Library, SINOMED, CNKI, and Wanfang databases. Statistical analysis and heterogeneity test were conducted by Review Manager 5.4. Results: Totally, 52 eligible studies were enrolled, including seven single nucleotide polymorphisms (SNPs) for four genes in the PI3K/AKT pathway (GNB3: rs5443; eNOS: rs1799983, rs869109213, rs2070744; IL‐6: rs1800795, rs1800796; TNFα: rs1800629). The "M" allele of eNOS rs1799983 was related to the increased risk of DKD under random effects model, especially in Asian population (Overall:M vs. W: I2 = 75%, OR = 1.29, 95%CI 1.07–1.56; MM + WM vs. WW: I2 = 75%, OR = 1.50, 95%CI 1.21–1.86). The "M" allele of eNOS rs869109213 was implicated with higher prevalence of DKD under random effects model, especially in Asian population (Overall:M vs. W: I2 = 63%, OR = 1.43, 95%CI 1.22–1.68; MM + WM vs. WW: I2 = 50%, OR = 1.36, 95%CI 1.16–1.58; MM vs. WM + WW: I2 = 59%, OR = 2.20, 95%CI 1.41–3.43). The "M" allele of eNOS rs2070744 was implicated with higher prevalence of DKD under random effects model, especially in Indian population (Overall: M vs. W: I2 = 47%, OR = 1.35, 95%CI 1.15–1.59; MM + WM vs. WW: I2 = 45%, OR = 1.32, 95%CI 1.07–1.62; MM vs. WM + WW: I2 = 65%, OR = 2.29, 95%CI 1.39–3.77). The "M" allele of IL‐6 rs1800796 was predominately associated with higher DKD risks under random effects model, especially in Asian population (Overall: M versus W: I2 = 23%, OR = 1.49, 95%CI 1.21–1.84; MM + WM vs. WW: I2 = 1%, OR = 1.43, 95%CI 1.15–1.77; MM + WM vs. WW: I2 = 71%, OR = 2.77, 95%CI 1.09–7.06). Conclusions: This meta‐analysis indicated that polymorphisms in the PI3K/Akt pathway in eNOS rs1799983, rs869109213, rs2070744, and IL‐6 rs1800796 were related to the increased risk of DKD. [ABSTRACT FROM AUTHOR]