Objective To develop an LC-MS/MS method for simultaneous determination of metolazone and valsartan in beagle dog plasma.Methods The chromatographic separation was achieved on an Agilent Poroshell 120(2.1 mm ×30 mm × 2.7 μm)analytical column.The multiple reaction monitoring mode operating in positive ion was adopted in MS detection, and precursors to the product ion transitions of m/z 366.2/259, 436.2/291 and 423.4/207 were used to measure metola-zone, valsartan and internal standard ( losartan potassium) .Results The method was linear over the concentration range of 0.5 ng/ml-100 ng/ml for metolazone and 5-5000 ng/ml for valsartan, with the correlation coefficients ( r2 ) of 0.9937 and 0.9939, respectively.The average intra-day precision values ( RSD) were 2.09% -8.85% for metolazone and 2.36%-13.12%for valsartan.The matrix effect values were 87.73%-98.62%for metolazone and 99.03%-137.35%for valsartan.The average recovery was 75.74%-81.82%for metolazone and 83.89%-95.64%for valsartan.Conclu-sion This analytical method for metolazone and valsartan is simple, accurate and sensitive, so it can be used for pharma-cokinetic research of metolazone and valsartan immediate release tablets in beagle dogs.

Spinal cord injuries is an extremely serious central nervous system injury. The clinical prognosis is very poor. Patients are often associated with lifelong disabilities or paralysis. Regulating NSCs to repair spinal cord injuries is unanimously considered to be a very potential option for the treatment of this type of disease. China has a large population and a large number of patients with spinal cord injuries. Actively regulating spinal cord NSCs is of great significance for the regeneration and repair of spinal cord injuries. Endogenous NSCs avoid many disadvantages of exogenous stem cell transplantation, and have a broader prospect in the treatment of spinal cord injuries. The Wnt signaling pathway plays a very important role in the differentiation of NSCs and the development of the nervous system. However, the molecular mechanism of the proliferation and differentiation of NSCs during regeneration and repair after spinal cord injuries is still not fully understood. This article mainly describes the research progress of Wnt pathway regulating NSCs in the regeneration and repair of spinal cord injuries.