A Simple and Rapid Liquid Chromatographic Method for the Determination of Major Metabolites of Sulfasalazine in Biological Fluids

Chungi, Vinod S.; Rekhi, Gurvinder Singh; Shargel, Leon

doi:10.1002/jps.2600780313

Cited by 41 publications

(20 citation statements)

References 10 publications

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“…22,23) Briefly, to determine the plasma concentration of SASP, each 100 ml plasma sample containing the internal standard (sulfamethoxazole 5 mg/ml (final concentration)) was added with 300 ml of methanol and mixed in a vortex mixer for 5 s. The mixture was stored on ice for 10 min, then centrifuged at 3000 rpm (950ϫg) for 2 min. Each 10 ml of the supernatant was subjected to the HPLC analysis.…”

Section: Methodsmentioning

confidence: 99%

N-Acetyltransferase 2 Genotype Correlates with Sulfasarazine Pharmacokinetics after Multiple Dosing in Healthy Japanese Subjects.

Kita

Sakaeda

Adachi

et al. 2001

Biological & Pharmaceutical Bulletin

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Sulfasalazine (SASP) has been commonly used in the treatment of inflammatory bowel diseases such as ulcerative colitis and Crohn's disease, and also in rheumatoid diseases.1,2) After ingestion, SASP is split into a sulfapyridine (SP) and a 5-aminosalicylic acid (5-ASA) component by bacterial azo reductases in the colon and cecum, followed by acetylation of SP into N-acetylsulfapyridine (AcSP) by polymorphic N-acetyltransferase 2 (NAT2) [EC 2.3.1.5] in the liver. [3][4][5] Downstream from SP to AcSP-Gluc was restricted by NAT2 being in Group II compared with Group I (Fig. 1). NAT2 activity has been diagnosed by phenotyping, that is, administration of a test drug and subsequent determination of its plasma concentration and/or urinary recovery, and the subjects have been stratified into rapid, intermediate and slow acetylators. [6][7][8] Due to the toxicity of SP, adverse effects after SASP administration have been more frequently found in slow acetylators than rapid acetylators.9-11) Dose individualization has been carried out according to the acetylator phenotype.The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method 12) was developed in the 1990's, which enabled the simple and rapid diagnosis of the protein function including NAT2 activity, compared with phenotyping. Patients need not to be exposed to any test drugs, and, therefore, it can be applied for dose individualization in routine patient care. [13][14][15][16][17] As for NAT2, it was demonstrated that the genotyping of three mutant alleles, NAT2*5B, NAT2*6A and NAT2*7B, was adequate to determine the acetylator phenotype by a correlation study using healthy subjects and single dosing. 13,14,[18][19][20] Rapid, intermediate and slow acetylator phenotypes were characterized by the homozygotes for the wild-type allele, the compound heterozygotes for the mutant allele, and the homozygotes for the mutant allele, respectively. This genotyping was expected to be promising in clinical applications, however, the effects of other factors arising from the clinical situation should be clarified including disease status, hepatic or renal functions, co-administered drugs, and multiple dosing, since these * To whom correspondence should be addressed. N-acetyltransferase 2 (NAT2) [EC 2.3.1.5]. In this study, the correlation between the NAT2 genotype and the pharmacokinetics of SP after multiple oral dosing of sulfasalazine (SASP) was examined to elucidate the effect of multiple dosing on the predictability of the phenotype by NAT2 genotyping. Seven healthy subjects were classified into two groups; the homozygotes for the wild-type allele, NAT2*4/*4 (Group I) and the compound heterozygotes for the mutant allele (NAT2*4/*6A or NAT2*4/*7B) (Group II). All received once-daily 1 g of SASP (Salazopyrin

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Section: Methodsmentioning

confidence: 99%

N-Acetyltransferase 2 Genotype Correlates with Sulfasarazine Pharmacokinetics after Multiple Dosing in Healthy Japanese Subjects.

Kita

Sakaeda

Adachi

et al. 2001

Biological & Pharmaceutical Bulletin

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“…[13][14][15][16] HPLC (LC-6A series, Shimadzu Co., Kyoto, Japan) consisted of a system controller (SCL-6B, Shimadzu), a variable wavelength ultraviolet detector (SPD-6AV, Shimadzu) adjusted to 260 nm, and a data processor (Chromatopac C-R4A, Shimadzu). The stationary phase was a reversed phase Chemcobond 5-ODS-H column (4.6 mm i.d.ϫ250 mm, particle size 5 mm, Chemco Chemical Co., Ltd., Osaka, Japan).…”

Section: N-acetyltransferase 2 Genotype-related Sulfapyridine Acetylamentioning

confidence: 99%

N-Acetyltransferase 2 Genotype-Related Sulfapyridine Acetylation and Its Adverse Events.

Kita

Aoyama

Gobara

et al. 2002

Biological & Pharmaceutical Bulletin

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Sulfasalazine (SASP) has been commonly used in the maintenance treatment for inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, and for rheumatoid disease. SASP is split into sulfapyridine (SP) and 5-aminosalicylic acid (5-ASA) components by bacterial azo reductases in the colon and caecum, followed by acetylation of SP into N-acetylsulfapyridine (AcSP) by polymorphic N-acetyltransferase 2 (NAT2) [EC 2.3.1.5] in the liver.3) 5-ASA was suggested to be effective for IBD, and SASP and SP are effective for rheumatoid disease. Adverse events such as nausea, vomiting, headache, malaise, hemolytic anaemia and reticulocytosis appear to be dependent on the serum SP concentration. [4][5][6][7][8] In contrast, a hypersensitivity reaction or those often found in an idiosyncratic manner at the initiation of therapy are independent of SASP dose, including skin rashes, aplastic anaemia, and hepatic and pulmonary dysfunction.7,9) NAT2 activity has been diagnosed by phenotyping; that is, examining plasma concentrations or urinary excretion profiles of tentatively administered test drugs, including isoniazid, caffeine and sulfamethazine (sulfadimidine), and the patients have been stratified into rapid, intermediate and slow acetylators. Based on the finding that adverse events after SASP administration have occurred more frequently with a slow acetylator than a rapid acetylator, dose individualization has been carried out according to NAT2 activity diagnosis by phenotyping to minimize the adverse events.In the 1990s, Deguchi et al. reported three point mutations in the NAT2 gene, and defined the wild-type allele NAT2*4 and three mutant alleles NAT2*5B, NAT2*6A and NAT2*7B.Patients can be stratified also by this genotyping into three groups: the homozygote for the wild-type allele NAT2*4/*4 (named Rapid Types), the compound heterozygote for the wild-type and mutant alleles

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“…The determination of 5-ASA has also been achieved in pharmaceutical formulation by cyclic voltammetry (Nigovi4 et al, 2001). There have been numerous publications describing the determination of 5-ASA in plasma or urine with ultraviolet or fluorimetric detection after liquid-liquid extraction with various organic solvents (Shaw et al, 1983;Chungi et al, 1989;Kringle et al, 1994;Clerici et al, 1994;Causon, 1997;Mahmud et al, 1999). Bystrowska et al (2000) have performed the determination of 5-ASA in plasma and urine samples Simultaneous assay of 5-aminosalicylic acid and its metabolite 351 ORIGINAL RESEARCH by liquid chromatography following prior derivatization to its acetylated metabolite.…”

Section: Introductionmentioning

confidence: 99%

A validated HPLC method with electrochemical detection for simultaneous assay of 5‐aminosalicylic acid and its metabolite in human plasma

Palumbo

Bacchi

Primavera

et al. 2004

Biomedical Chromatography

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A high-performance liquid chromatographic method was developed, validated and applied to the simultaneous determination of 5-aminosalicylic acid (5-ASA) and its acetylated metabolite (acetyl-5-ASA) in human plasma. The method involves liquid-liquid extraction with methanol followed by isocratic reversed-phase chromatography on a Kromasil KR100 C(18) column with electrochemical detection. The recovery, selectivity, linearity, precision and accuracy of the method were evaluated from spiked human plasma samples. The effects of mobile phase composition, buffer concentration, mobile phase pH and concentration of organic modifiers on retention of 5-ASA, acetyl 5-ASA and internal standard were investigated. Limits' of detection were 5 ng/mL for 5-ASA and 10 ng/mL for acetyl-5-ASA, respectively. The method can be used for supporting therapeutical drug monitoring and pharmacokinetic studies.

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A Simple and Rapid Liquid Chromatographic Method for the Determination of Major Metabolites of Sulfasalazine in Biological Fluids

Cited by 41 publications

References 10 publications

N-Acetyltransferase 2 Genotype Correlates with Sulfasarazine Pharmacokinetics after Multiple Dosing in Healthy Japanese Subjects.

N-Acetyltransferase 2 Genotype Correlates with Sulfasarazine Pharmacokinetics after Multiple Dosing in Healthy Japanese Subjects.

N-Acetyltransferase 2 Genotype-Related Sulfapyridine Acetylation and Its Adverse Events.

A validated HPLC method with electrochemical detection for simultaneous assay of 5‐aminosalicylic acid and its metabolite in human plasma

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